THE CASE

A 36-year-old man sought care at our family medicine clinic for knee pain that he’d had for the past year. He denied any previous injury or trauma to the knee. The pain affected the posterolateral left knee and was aggravated by squatting and deep flexion. Daily activities did not bother him, but skiing, golfing, mountain biking, and lifting weights worsened the pain. His pain had gradually become more severe and frequent. He denied any mechanical symptoms such as catching, popping, or locking.

Examination of his left knee demonstrated range of motion from 0 to 120 degrees; further flexion caused significant pain. McMurray and Thessaly tests were positive for posterolateral pain, particularly with knee flexion >120 degrees. Physical examination was otherwise unremarkable. Standard x-rays of the left knee were normal. Our patient completed a month of physical therapy, but his symptoms did not improve.

THE DIAGNOSIS

After the patient completed physical therapy, magnetic resonance imaging (MRI) was performed. The MRI did not reveal any left knee effusion, and the menisci, collateral ligaments, and cartilage surfaces were normal. And, while the cruciate ligaments were intact, a large pericruciate ganglion cyst was noted (FIGURES 1 AND 2).

DISCUSSION

Ganglion cysts are dense, encapsulated structures filled with clear viscous fluid that often arise adjacent to tendon sheaths or joint capsules, most commonly over the dorsum of the hand.¹ Intra-articular ganglia involving the cruciate ligaments of the knee are relatively uncommon.² The estimated prevalence of cruciate ligament ganglion cysts at arthroscopy is 0.2% to 1.9%; similar rates have been demonstrated with MRI.^3-6 There are more reported cases of these cysts involving the anterior cruciate ligament (ACL) compared to those affecting the posterior cruciate ligament (PCL).^2,6

Classification of these cysts is based on relative location with respect to the ligaments. Type 1 cysts originate anterior to the ACL; type 2, between the ACL and PCL; and type 3, posterior to the PCL.^6,7 Cruciate ligament ganglion cysts are more common in men, are typically discovered between age 20 and 40, and are usually incidental findings.⁸

The pathogenesis of ganglion cyst formation is unknown.^1,6,7 The most widely accepted theory is that ganglion cysts result from mucinous degeneration of connective tissue in areas of repetitive stress.^1,6,7 Other theories suggest hyaluronic acid production secondary to mesenchymal stem cell proliferation within the ligaments, synovial tissue herniation, or congenital translocation of synovial tissue as possible etiologies.^2,6,7

Concurrent pathologies such as meniscal tears or chondral lesions may also be present; however, there is some disagreement as to what role, if any, antecedent trauma has in the pathogenesis of cyst formation.^1,6 Several investigators have suggested that prior knee trauma is a likely risk factor.^2,8,9 

In most patients, cruciate ligament ganglion cysts are asymptomatic.⁷ The most common presenting symptom is nonspecific pain that is exacerbated by activity, such as stair climbing, squatting, or other activities that require extreme flexion or extension of the knee.^6,9 Other possible symptoms include limited range of motion (extension block with ACL involvement, limited flexion with PCL lesions), a catching or locking sensation, instability, or joint line tenderness.^5,6 A palpable mass on physical exam is not usually present.⁶ Some investigators suggest that larger lesions and those closer to the femoral ligamentous attachments are more likely to cause symptoms.⁵

Cruciate ligament ganglion cysts can be an easily overlooked source of a patient’s symptoms because they often mimic more common pathologies.² The differential diagnosis of cruciate ligament ganglion cysts and posterior knee pain includes any other intra-articular cysts (eg, meniscal cysts), posterior meniscal tear, popliteus tendinopathy, or neoplasms (eg, hemangioma and synovial sarcoma).^2,6

MRI is the best method of diagnosis

Because the symptoms of cruciate ligament ganglion cysts are variable and nonspecific, the diagnosis is rarely made on clinical grounds alone.¹ The best method of evaluating suspected intra-articular pathologies such as cruciate ligament ganglion cysts is MRI.^5,10

Cruciate ligament ganglion cysts are more common in men and are usually incidental findings.

Cruciate ligament ganglion cysts typically follow fluid signal on all sequences, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^1,2,5,6 A pericruciate location with a multilocular appearance is usually sufficient evidence to make a diagnosis. However, solid or semi-solid pathologies (such as synovial cell sarcoma, synovial hemangioma, or synovial chondromatosis) can have similar signal intensity.

If necessary, intravenous contrast can be helpful; a lack of central contrast enhancement can differentiate ganglion cysts from other solid, enhancing, or partially enhancing lesions. Other diagnostic modalities, such as ultrasound, computed tomography (CT), and diagnostic arthroscopy, are less practical and have a wide range of sensitivity and specificity.^5,6,10

Arthroscopic excision is the treatment of choice

Asymptomatic cruciate ligament ganglion cysts are usually managed with clinical follow-up. For patients with symptomatic cysts, ultrasound- or CT-guided percutaneous cyst aspiration may temporarily improve symptoms, but recurrence rates have not been well studied.^2,6,9,10 Additionally, accessibility to cysts in this location via these approaches is limited. Arthroscopic excision of the cyst is the treatment of choice for symptomatic cases.^1,2,5,6,10

Our patient underwent arthroscopic cyst resection, which resulted in complete resolution of his symptoms. In 3 months, he returned to his regular physical activities with no pain or discomfort. One year later, he remained asymptomatic.

THE TAKEAWAY

Cruciate ligament ganglion cysts are a rare cause of posterior knee pain. An MRI is the best diagnostic modality to evaluate and confirm the diagnosis, as well as rule out other pathologies. The treatment of choice for symptomatic cases is arthroscopic excision of the cyst.

THE CASE

A 36-year-old man sought care at our family medicine clinic for knee pain that he’d had for the past year. He denied any previous injury or trauma to the knee. The pain affected the posterolateral left knee and was aggravated by squatting and deep flexion. Daily activities did not bother him, but skiing, golfing, mountain biking, and lifting weights worsened the pain. His pain had gradually become more severe and frequent. He denied any mechanical symptoms such as catching, popping, or locking.

Examination of his left knee demonstrated range of motion from 0 to 120 degrees; further flexion caused significant pain. McMurray and Thessaly tests were positive for posterolateral pain, particularly with knee flexion >120 degrees. Physical examination was otherwise unremarkable. Standard x-rays of the left knee were normal. Our patient completed a month of physical therapy, but his symptoms did not improve.

THE DIAGNOSIS

After the patient completed physical therapy, magnetic resonance imaging (MRI) was performed. The MRI did not reveal any left knee effusion, and the menisci, collateral ligaments, and cartilage surfaces were normal. And, while the cruciate ligaments were intact, a large pericruciate ganglion cyst was noted (FIGURES 1 AND 2).

DISCUSSION

Ganglion cysts are dense, encapsulated structures filled with clear viscous fluid that often arise adjacent to tendon sheaths or joint capsules, most commonly over the dorsum of the hand.¹ Intra-articular ganglia involving the cruciate ligaments of the knee are relatively uncommon.² The estimated prevalence of cruciate ligament ganglion cysts at arthroscopy is 0.2% to 1.9%; similar rates have been demonstrated with MRI.^3-6 There are more reported cases of these cysts involving the anterior cruciate ligament (ACL) compared to those affecting the posterior cruciate ligament (PCL).^2,6

Classification of these cysts is based on relative location with respect to the ligaments. Type 1 cysts originate anterior to the ACL; type 2, between the ACL and PCL; and type 3, posterior to the PCL.^6,7 Cruciate ligament ganglion cysts are more common in men, are typically discovered between age 20 and 40, and are usually incidental findings.⁸

The pathogenesis of ganglion cyst formation is unknown.^1,6,7 The most widely accepted theory is that ganglion cysts result from mucinous degeneration of connective tissue in areas of repetitive stress.^1,6,7 Other theories suggest hyaluronic acid production secondary to mesenchymal stem cell proliferation within the ligaments, synovial tissue herniation, or congenital translocation of synovial tissue as possible etiologies.^2,6,7

Concurrent pathologies such as meniscal tears or chondral lesions may also be present; however, there is some disagreement as to what role, if any, antecedent trauma has in the pathogenesis of cyst formation.^1,6 Several investigators have suggested that prior knee trauma is a likely risk factor.^2,8,9 

In most patients, cruciate ligament ganglion cysts are asymptomatic.⁷ The most common presenting symptom is nonspecific pain that is exacerbated by activity, such as stair climbing, squatting, or other activities that require extreme flexion or extension of the knee.^6,9 Other possible symptoms include limited range of motion (extension block with ACL involvement, limited flexion with PCL lesions), a catching or locking sensation, instability, or joint line tenderness.^5,6 A palpable mass on physical exam is not usually present.⁶ Some investigators suggest that larger lesions and those closer to the femoral ligamentous attachments are more likely to cause symptoms.⁵

Cruciate ligament ganglion cysts can be an easily overlooked source of a patient’s symptoms because they often mimic more common pathologies.² The differential diagnosis of cruciate ligament ganglion cysts and posterior knee pain includes any other intra-articular cysts (eg, meniscal cysts), posterior meniscal tear, popliteus tendinopathy, or neoplasms (eg, hemangioma and synovial sarcoma).^2,6

MRI is the best method of diagnosis

Because the symptoms of cruciate ligament ganglion cysts are variable and nonspecific, the diagnosis is rarely made on clinical grounds alone.¹ The best method of evaluating suspected intra-articular pathologies such as cruciate ligament ganglion cysts is MRI.^5,10

Cruciate ligament ganglion cysts are more common in men and are usually incidental findings.

Cruciate ligament ganglion cysts typically follow fluid signal on all sequences, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^1,2,5,6 A pericruciate location with a multilocular appearance is usually sufficient evidence to make a diagnosis. However, solid or semi-solid pathologies (such as synovial cell sarcoma, synovial hemangioma, or synovial chondromatosis) can have similar signal intensity.

If necessary, intravenous contrast can be helpful; a lack of central contrast enhancement can differentiate ganglion cysts from other solid, enhancing, or partially enhancing lesions. Other diagnostic modalities, such as ultrasound, computed tomography (CT), and diagnostic arthroscopy, are less practical and have a wide range of sensitivity and specificity.^5,6,10

Arthroscopic excision is the treatment of choice

Asymptomatic cruciate ligament ganglion cysts are usually managed with clinical follow-up. For patients with symptomatic cysts, ultrasound- or CT-guided percutaneous cyst aspiration may temporarily improve symptoms, but recurrence rates have not been well studied.^2,6,9,10 Additionally, accessibility to cysts in this location via these approaches is limited. Arthroscopic excision of the cyst is the treatment of choice for symptomatic cases.^1,2,5,6,10

Our patient underwent arthroscopic cyst resection, which resulted in complete resolution of his symptoms. In 3 months, he returned to his regular physical activities with no pain or discomfort. One year later, he remained asymptomatic.

THE TAKEAWAY

Cruciate ligament ganglion cysts are a rare cause of posterior knee pain. An MRI is the best diagnostic modality to evaluate and confirm the diagnosis, as well as rule out other pathologies. The treatment of choice for symptomatic cases is arthroscopic excision of the cyst.

THE CASE

A 36-year-old man sought care at our family medicine clinic for knee pain that he’d had for the past year. He denied any previous injury or trauma to the knee. The pain affected the posterolateral left knee and was aggravated by squatting and deep flexion. Daily activities did not bother him, but skiing, golfing, mountain biking, and lifting weights worsened the pain. His pain had gradually become more severe and frequent. He denied any mechanical symptoms such as catching, popping, or locking.

Examination of his left knee demonstrated range of motion from 0 to 120 degrees; further flexion caused significant pain. McMurray and Thessaly tests were positive for posterolateral pain, particularly with knee flexion >120 degrees. Physical examination was otherwise unremarkable. Standard x-rays of the left knee were normal. Our patient completed a month of physical therapy, but his symptoms did not improve.

THE DIAGNOSIS

After the patient completed physical therapy, magnetic resonance imaging (MRI) was performed. The MRI did not reveal any left knee effusion, and the menisci, collateral ligaments, and cartilage surfaces were normal. And, while the cruciate ligaments were intact, a large pericruciate ganglion cyst was noted (FIGURES 1 AND 2).

DISCUSSION

Ganglion cysts are dense, encapsulated structures filled with clear viscous fluid that often arise adjacent to tendon sheaths or joint capsules, most commonly over the dorsum of the hand.¹ Intra-articular ganglia involving the cruciate ligaments of the knee are relatively uncommon.² The estimated prevalence of cruciate ligament ganglion cysts at arthroscopy is 0.2% to 1.9%; similar rates have been demonstrated with MRI.^3-6 There are more reported cases of these cysts involving the anterior cruciate ligament (ACL) compared to those affecting the posterior cruciate ligament (PCL).^2,6

Classification of these cysts is based on relative location with respect to the ligaments. Type 1 cysts originate anterior to the ACL; type 2, between the ACL and PCL; and type 3, posterior to the PCL.^6,7 Cruciate ligament ganglion cysts are more common in men, are typically discovered between age 20 and 40, and are usually incidental findings.⁸

The pathogenesis of ganglion cyst formation is unknown.^1,6,7 The most widely accepted theory is that ganglion cysts result from mucinous degeneration of connective tissue in areas of repetitive stress.^1,6,7 Other theories suggest hyaluronic acid production secondary to mesenchymal stem cell proliferation within the ligaments, synovial tissue herniation, or congenital translocation of synovial tissue as possible etiologies.^2,6,7

Concurrent pathologies such as meniscal tears or chondral lesions may also be present; however, there is some disagreement as to what role, if any, antecedent trauma has in the pathogenesis of cyst formation.^1,6 Several investigators have suggested that prior knee trauma is a likely risk factor.^2,8,9 

In most patients, cruciate ligament ganglion cysts are asymptomatic.⁷ The most common presenting symptom is nonspecific pain that is exacerbated by activity, such as stair climbing, squatting, or other activities that require extreme flexion or extension of the knee.^6,9 Other possible symptoms include limited range of motion (extension block with ACL involvement, limited flexion with PCL lesions), a catching or locking sensation, instability, or joint line tenderness.^5,6 A palpable mass on physical exam is not usually present.⁶ Some investigators suggest that larger lesions and those closer to the femoral ligamentous attachments are more likely to cause symptoms.⁵

Cruciate ligament ganglion cysts can be an easily overlooked source of a patient’s symptoms because they often mimic more common pathologies.² The differential diagnosis of cruciate ligament ganglion cysts and posterior knee pain includes any other intra-articular cysts (eg, meniscal cysts), posterior meniscal tear, popliteus tendinopathy, or neoplasms (eg, hemangioma and synovial sarcoma).^2,6

MRI is the best method of diagnosis

Because the symptoms of cruciate ligament ganglion cysts are variable and nonspecific, the diagnosis is rarely made on clinical grounds alone.¹ The best method of evaluating suspected intra-articular pathologies such as cruciate ligament ganglion cysts is MRI.^5,10

Cruciate ligament ganglion cysts are more common in men and are usually incidental findings.

Cruciate ligament ganglion cysts typically follow fluid signal on all sequences, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^1,2,5,6 A pericruciate location with a multilocular appearance is usually sufficient evidence to make a diagnosis. However, solid or semi-solid pathologies (such as synovial cell sarcoma, synovial hemangioma, or synovial chondromatosis) can have similar signal intensity.

If necessary, intravenous contrast can be helpful; a lack of central contrast enhancement can differentiate ganglion cysts from other solid, enhancing, or partially enhancing lesions. Other diagnostic modalities, such as ultrasound, computed tomography (CT), and diagnostic arthroscopy, are less practical and have a wide range of sensitivity and specificity.^5,6,10

Arthroscopic excision is the treatment of choice

Asymptomatic cruciate ligament ganglion cysts are usually managed with clinical follow-up. For patients with symptomatic cysts, ultrasound- or CT-guided percutaneous cyst aspiration may temporarily improve symptoms, but recurrence rates have not been well studied.^2,6,9,10 Additionally, accessibility to cysts in this location via these approaches is limited. Arthroscopic excision of the cyst is the treatment of choice for symptomatic cases.^1,2,5,6,10

Our patient underwent arthroscopic cyst resection, which resulted in complete resolution of his symptoms. In 3 months, he returned to his regular physical activities with no pain or discomfort. One year later, he remained asymptomatic.

THE TAKEAWAY

Cruciate ligament ganglion cysts are a rare cause of posterior knee pain. An MRI is the best diagnostic modality to evaluate and confirm the diagnosis, as well as rule out other pathologies. The treatment of choice for symptomatic cases is arthroscopic excision of the cyst.

THE CASES

CASE 1 ›  A 15-month-old boy was brought to our center for plastic surgery after being referred by his general practitioner (GP). The patient had a non-healing lesion on his umbilicus that had been present since birth. It had remained the same size, but bled occasionally. The GP initially presumed the lesion was a granuloma and treated it with silver nitrate cautery, but this did not eradicate it.

After talking with the boy’s mother further, we learned that there had been a constant oozing from the area since birth and that the lesion protruded slightly from the abdomen when the child cried. The boy had congenital heart disease, but his bowel and genitourinary history were normal. A clinical examination revealed pink, moist tissue herniating from the umbilicus with surrounding abdominal fullness when the boy stood up (FIGURE 1A). An ultrasound showed a focal 19 x 7 mm complex area around the umbilicus with no definite track. The lesion was surgically removed. Histology revealed a completely excised vitellointestinal duct remnant.

CASE 2 ›  A 6-year-old boy with a history of attention-deficit/hyperactivity disorder was brought to our clinic with a non-healing umbilical lesion after being referred by his GP. The lesion had been present since birth and had failed to resolve despite several attempts to treat it with silver nitrate cautery. Clinically, the patient appeared to have a granulomatous umbilical polyp (FIGURE 1B). The patient underwent surgical excision of the lesion. Histological analysis revealed a completely excised vitellointestinal duct remnant (FIGURE 2).

DISCUSSION

The vitellointestinal duct (VID), also called the omphalomesenteric duct (OMD), connects the alimentary canal and the yolk sac in early embryogenesis. Failure of involution of the duct results in abnormalities such as Meckel’s diverticulum, cysts, and polyps.

VID anomalies occur in approximately 2% of newborns; a small percentage of these have patent connections to the intestine.¹ Parents are often the first to notice the abnormality and will typically see a reddish protrusion around the umbilicus or a persistent serous discharge around the umbilicus soon after birth.

VID remnants are similar in presentation to benign granulomas or granulation tissue, which are benign lesions that present in the first few weeks of life. Granulomas are reddish in color, bleed minimally when irritated by trauma, and respond well to silver nitrate cautery.² When the lesion fails to respond to treatment, an alternative diagnosis should be investigated further.

Ultrasonography is the best way to evaluate a suspected VID remnant

A suspected VID remnant should first be assessed with ultrasonography to determine the extent of the remnant and guide surgical treatment. Ultrasonography can also delineate the relationship of these congenital remnants with the umbilicus and bladder.³

Potential complications that can arise from these lesions include an intestinal hernia, intussusception, volvulus, abdominal pain, or a persistent discharge that can lead to infection.³ Mortality following complications is significantly high.⁴

Although the etiology of patent VIDs and their remnants remains unknown, the presence of such ducts is associated with other congenital anomalies, including Down Syndrome, structural cardiac malformation, conduction abnormalities, and cleft lip and palate.^5-7 Therefore, additional history taking and examinations may be required to identify these associated pathologies. In Case 1, the 15-month-old boy had congenital heart disease.

Surgical excision will prevent complications

A simple surgical excision should be performed for VID remnants. The prognosis is excellent when such procedures are performed in the non-acute setting. Some debate exists as to whether all remnants require formal abdominal exploration.^8,9

Treatment of patent VIDs requires surgical excision of the duct, with or without a segment of the small bowel, to obliterate the connection.¹⁰ Reconstruction of the umbilicus is then performed, depending on the surgical technique used.

Vitellointestinal duct remnants are similar in presentation to benign granulomasor granulation tissue.

Our patients both made complete recoveries following their surgeries with resolution of their symptoms.

THE TAKEAWAY

Consider a VID remnant as part of the differential diagnosis for any patient who has what appears to be a granulomatous umbilical lesion. Order ultrasonography to evaluate a suspected VID, especially for lesions that fail to respond to 2 or 3 silver nitrate treatments. Surgical excision of a VID remnant is usually curative.

THE CASES

CASE 1 ›  A 15-month-old boy was brought to our center for plastic surgery after being referred by his general practitioner (GP). The patient had a non-healing lesion on his umbilicus that had been present since birth. It had remained the same size, but bled occasionally. The GP initially presumed the lesion was a granuloma and treated it with silver nitrate cautery, but this did not eradicate it.

After talking with the boy’s mother further, we learned that there had been a constant oozing from the area since birth and that the lesion protruded slightly from the abdomen when the child cried. The boy had congenital heart disease, but his bowel and genitourinary history were normal. A clinical examination revealed pink, moist tissue herniating from the umbilicus with surrounding abdominal fullness when the boy stood up (FIGURE 1A). An ultrasound showed a focal 19 x 7 mm complex area around the umbilicus with no definite track. The lesion was surgically removed. Histology revealed a completely excised vitellointestinal duct remnant.

CASE 2 ›  A 6-year-old boy with a history of attention-deficit/hyperactivity disorder was brought to our clinic with a non-healing umbilical lesion after being referred by his GP. The lesion had been present since birth and had failed to resolve despite several attempts to treat it with silver nitrate cautery. Clinically, the patient appeared to have a granulomatous umbilical polyp (FIGURE 1B). The patient underwent surgical excision of the lesion. Histological analysis revealed a completely excised vitellointestinal duct remnant (FIGURE 2).

DISCUSSION

The vitellointestinal duct (VID), also called the omphalomesenteric duct (OMD), connects the alimentary canal and the yolk sac in early embryogenesis. Failure of involution of the duct results in abnormalities such as Meckel’s diverticulum, cysts, and polyps.

VID anomalies occur in approximately 2% of newborns; a small percentage of these have patent connections to the intestine.¹ Parents are often the first to notice the abnormality and will typically see a reddish protrusion around the umbilicus or a persistent serous discharge around the umbilicus soon after birth.

VID remnants are similar in presentation to benign granulomas or granulation tissue, which are benign lesions that present in the first few weeks of life. Granulomas are reddish in color, bleed minimally when irritated by trauma, and respond well to silver nitrate cautery.² When the lesion fails to respond to treatment, an alternative diagnosis should be investigated further.

Ultrasonography is the best way to evaluate a suspected VID remnant

A suspected VID remnant should first be assessed with ultrasonography to determine the extent of the remnant and guide surgical treatment. Ultrasonography can also delineate the relationship of these congenital remnants with the umbilicus and bladder.³

Potential complications that can arise from these lesions include an intestinal hernia, intussusception, volvulus, abdominal pain, or a persistent discharge that can lead to infection.³ Mortality following complications is significantly high.⁴

Although the etiology of patent VIDs and their remnants remains unknown, the presence of such ducts is associated with other congenital anomalies, including Down Syndrome, structural cardiac malformation, conduction abnormalities, and cleft lip and palate.^5-7 Therefore, additional history taking and examinations may be required to identify these associated pathologies. In Case 1, the 15-month-old boy had congenital heart disease.

Surgical excision will prevent complications

A simple surgical excision should be performed for VID remnants. The prognosis is excellent when such procedures are performed in the non-acute setting. Some debate exists as to whether all remnants require formal abdominal exploration.^8,9

Treatment of patent VIDs requires surgical excision of the duct, with or without a segment of the small bowel, to obliterate the connection.¹⁰ Reconstruction of the umbilicus is then performed, depending on the surgical technique used.

Vitellointestinal duct remnants are similar in presentation to benign granulomasor granulation tissue.

Our patients both made complete recoveries following their surgeries with resolution of their symptoms.

THE TAKEAWAY

Consider a VID remnant as part of the differential diagnosis for any patient who has what appears to be a granulomatous umbilical lesion. Order ultrasonography to evaluate a suspected VID, especially for lesions that fail to respond to 2 or 3 silver nitrate treatments. Surgical excision of a VID remnant is usually curative.

THE CASES

CASE 1 ›  A 15-month-old boy was brought to our center for plastic surgery after being referred by his general practitioner (GP). The patient had a non-healing lesion on his umbilicus that had been present since birth. It had remained the same size, but bled occasionally. The GP initially presumed the lesion was a granuloma and treated it with silver nitrate cautery, but this did not eradicate it.

After talking with the boy’s mother further, we learned that there had been a constant oozing from the area since birth and that the lesion protruded slightly from the abdomen when the child cried. The boy had congenital heart disease, but his bowel and genitourinary history were normal. A clinical examination revealed pink, moist tissue herniating from the umbilicus with surrounding abdominal fullness when the boy stood up (FIGURE 1A). An ultrasound showed a focal 19 x 7 mm complex area around the umbilicus with no definite track. The lesion was surgically removed. Histology revealed a completely excised vitellointestinal duct remnant.

CASE 2 ›  A 6-year-old boy with a history of attention-deficit/hyperactivity disorder was brought to our clinic with a non-healing umbilical lesion after being referred by his GP. The lesion had been present since birth and had failed to resolve despite several attempts to treat it with silver nitrate cautery. Clinically, the patient appeared to have a granulomatous umbilical polyp (FIGURE 1B). The patient underwent surgical excision of the lesion. Histological analysis revealed a completely excised vitellointestinal duct remnant (FIGURE 2).

DISCUSSION

The vitellointestinal duct (VID), also called the omphalomesenteric duct (OMD), connects the alimentary canal and the yolk sac in early embryogenesis. Failure of involution of the duct results in abnormalities such as Meckel’s diverticulum, cysts, and polyps.

VID anomalies occur in approximately 2% of newborns; a small percentage of these have patent connections to the intestine.¹ Parents are often the first to notice the abnormality and will typically see a reddish protrusion around the umbilicus or a persistent serous discharge around the umbilicus soon after birth.

VID remnants are similar in presentation to benign granulomas or granulation tissue, which are benign lesions that present in the first few weeks of life. Granulomas are reddish in color, bleed minimally when irritated by trauma, and respond well to silver nitrate cautery.² When the lesion fails to respond to treatment, an alternative diagnosis should be investigated further.

Ultrasonography is the best way to evaluate a suspected VID remnant

A suspected VID remnant should first be assessed with ultrasonography to determine the extent of the remnant and guide surgical treatment. Ultrasonography can also delineate the relationship of these congenital remnants with the umbilicus and bladder.³

Potential complications that can arise from these lesions include an intestinal hernia, intussusception, volvulus, abdominal pain, or a persistent discharge that can lead to infection.³ Mortality following complications is significantly high.⁴

Although the etiology of patent VIDs and their remnants remains unknown, the presence of such ducts is associated with other congenital anomalies, including Down Syndrome, structural cardiac malformation, conduction abnormalities, and cleft lip and palate.^5-7 Therefore, additional history taking and examinations may be required to identify these associated pathologies. In Case 1, the 15-month-old boy had congenital heart disease.

Surgical excision will prevent complications

A simple surgical excision should be performed for VID remnants. The prognosis is excellent when such procedures are performed in the non-acute setting. Some debate exists as to whether all remnants require formal abdominal exploration.^8,9

Treatment of patent VIDs requires surgical excision of the duct, with or without a segment of the small bowel, to obliterate the connection.¹⁰ Reconstruction of the umbilicus is then performed, depending on the surgical technique used.

Vitellointestinal duct remnants are similar in presentation to benign granulomasor granulation tissue.

Our patients both made complete recoveries following their surgeries with resolution of their symptoms.

THE TAKEAWAY

Consider a VID remnant as part of the differential diagnosis for any patient who has what appears to be a granulomatous umbilical lesion. Order ultrasonography to evaluate a suspected VID, especially for lesions that fail to respond to 2 or 3 silver nitrate treatments. Surgical excision of a VID remnant is usually curative.

For some time, electronic health records (EHRs) have been the focus of many articles (“EHR use and patient satisfaction: What we learned.” J Fam Pract. 2015;64:687-696) and the source of great debate (and frustration) in the health care community. But there’s a logical solution to the dilemmas created by EHRs: A team-based care model.¹

A fundamental principle of team-based care is that all members of the team work at the top of their skill set. So, with that in mind, most of the duties of EHR management should be delegated to other team members, rather than to the physicians. In our system, every physician works with 2 other people—certified medical assistants or licensed practical nurses—who help with standing orders, protocols, templates, and many of the EHR duties, including a significant portion of team documentation. They do this while recognizing and respecting guidelines from the Centers for Medicare & Medicaid Services and other payers. That leaves the physicians and advanced practice clinicians the time they need to focus on the patient during the visit.

Not surprisingly, patient satisfaction, staff satisfaction, and quality measures are all improving with this model of care. It is proving financially viable, as well. This model may well be the future of health care delivery for office-based practices.²

Jim Jerzak, MD
Green Bay, Wis

1. Sinsky CA, Willard-Grace R, Schutzbank AM, et al. In search of joy in practice: a report of 23 high-functioning primary care practices. Ann Fam Med. 2013;11:272-278.

2. Ghorob A, Bodenheimer T. Building teams in primary care: A practical guide. Fam Syst Health. 2015;33:182-192.

For some time, electronic health records (EHRs) have been the focus of many articles (“EHR use and patient satisfaction: What we learned.” J Fam Pract. 2015;64:687-696) and the source of great debate (and frustration) in the health care community. But there’s a logical solution to the dilemmas created by EHRs: A team-based care model.¹

A fundamental principle of team-based care is that all members of the team work at the top of their skill set. So, with that in mind, most of the duties of EHR management should be delegated to other team members, rather than to the physicians. In our system, every physician works with 2 other people—certified medical assistants or licensed practical nurses—who help with standing orders, protocols, templates, and many of the EHR duties, including a significant portion of team documentation. They do this while recognizing and respecting guidelines from the Centers for Medicare & Medicaid Services and other payers. That leaves the physicians and advanced practice clinicians the time they need to focus on the patient during the visit.

Not surprisingly, patient satisfaction, staff satisfaction, and quality measures are all improving with this model of care. It is proving financially viable, as well. This model may well be the future of health care delivery for office-based practices.²

Jim Jerzak, MD
Green Bay, Wis

1. Sinsky CA, Willard-Grace R, Schutzbank AM, et al. In search of joy in practice: a report of 23 high-functioning primary care practices. Ann Fam Med. 2013;11:272-278.

2. Ghorob A, Bodenheimer T. Building teams in primary care: A practical guide. Fam Syst Health. 2015;33:182-192.

For some time, electronic health records (EHRs) have been the focus of many articles (“EHR use and patient satisfaction: What we learned.” J Fam Pract. 2015;64:687-696) and the source of great debate (and frustration) in the health care community. But there’s a logical solution to the dilemmas created by EHRs: A team-based care model.¹

A fundamental principle of team-based care is that all members of the team work at the top of their skill set. So, with that in mind, most of the duties of EHR management should be delegated to other team members, rather than to the physicians. In our system, every physician works with 2 other people—certified medical assistants or licensed practical nurses—who help with standing orders, protocols, templates, and many of the EHR duties, including a significant portion of team documentation. They do this while recognizing and respecting guidelines from the Centers for Medicare & Medicaid Services and other payers. That leaves the physicians and advanced practice clinicians the time they need to focus on the patient during the visit.

Not surprisingly, patient satisfaction, staff satisfaction, and quality measures are all improving with this model of care. It is proving financially viable, as well. This model may well be the future of health care delivery for office-based practices.²

Jim Jerzak, MD
Green Bay, Wis

1. Sinsky CA, Willard-Grace R, Schutzbank AM, et al. In search of joy in practice: a report of 23 high-functioning primary care practices. Ann Fam Med. 2013;11:272-278.

2. Ghorob A, Bodenheimer T. Building teams in primary care: A practical guide. Fam Syst Health. 2015;33:182-192.

Personality disorders (PDs) are common, affecting up to 15% of US adults, and are associated with comorbid medical and psychiatric conditions and increased utilization of health care resources.^1,2 Having a basic understanding of these patterns of thinking and behaving can help family physicians (FPs) identify specific PD diagnoses, ensure appropriate treatment, and reduce the frustration that arises when an individual is viewed as a “difficult patient.”

Here we describe the diagnostic features of the disorders in the 3 major clusters of PDs and review an effective approach to the management of the most common disorder in each cluster, using a case study patient.

Defense mechanisms offer clues that your patient may have a PD

Personality is an enduring pattern of inner experience and behaviors that is relatively stable across time and in different situations. Such traits comprise an individual’s inherent makeup.¹ PDs are diagnosed when an individual’s personality traits create significant distress or impairment in daily functioning. Specifically, PDs have a negative impact on cognition, affect, interpersonal relationships, and/or impulse control.¹

One of the ways people alleviate distress is by using defense mechanisms. Defense mechanisms are unconscious mental processes that individuals use to resolve conflicts, and thereby reduce anxiety and depression on a conscious level. Taken alone, defense mechanisms are not pathologic, but they may become maladaptive in certain stressful circumstances, such as when receiving medical treatment. Recognizing patterns of chronic use of certain defense mechanisms may be a clue that your patient has a PD. TABLE 1^3,4 and TABLE 2^3,4 provide an overview of common defense mechanisms used by patients with PDs.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) organizes PDs into 3 clusters based on similar and often overlapping symptoms.¹TABLE 3¹ provides a brief summary of the characteristic features of each disorder in these clusters.

Cluster A: Odd, eccentric

Patients with one of these disorders are odd, eccentric, or bizarre in their behavior and thinking. There appears to be a genetic link between cluster A PDs (especially schizotypal) and schizophrenia.⁵ These patients rarely seek treatment for their disorder because they have limited insight into their maladaptive traits.^5,6

CASE 1 › Daniel A, age 57, has hypertension and hyperlipidemia and comes in to see his FP for a 6-month follow-up appointment. He never misses appointments, but has a history of poor adherence with prescribed medications. He enjoys his discussions with you in the office, although he often perseverates on conspiracy theories. He lives alone and has never been married. He believes that some of the previously prescribed medications, including a statin and a thiazide diuretic, were interfering with the absorption of “positive nutrients” in his diet. He also refuses to take the generic form of a statin, which he believes was adulterated by the government to be sold at lower cost.

Mr. A demonstrates the odd and eccentric beliefs that characterize schizotypal personality disorder. How can his FP best help him adhere to his medication regimen? (For the answer, click here.)

Schizotypal personality disorder shares certain disturbances of thought with schizophrenia, and is believed to exist on a spectrum with other primary psychotic disorders. Support for this theory comes from the higher rates of schizotypal PD among family members of patients with schizophrenia. There is a genetic component to the disorder.^3,5,6

Clinically, these patients appear odd and eccentric with unusual beliefs. They may have a fascination with magic, clairvoyance, telepathy, or other such notions.^1,5 Although the perceptual disturbances are unusual and often bizarre, they are not frank delusions: patients with schizotypal PD are willing to consider alternative explanations for their beliefs and can engage in rational discussion. Cognitive deficits, particularly of memory and attention, are common and distressing to patients. Frequently, the presenting complaint is depression and anxiety due to the emotional discord and isolation from others.^1,3,5,6

Continue to cluster B >>

Cluster B: Dramatic, erratic

Does your patient complain that you don't understand him "the way his other doctor did"? Or does he frequently lose his temper? Perhaps it's time to consider a personality disorder.

Patients with cluster B PDs are dramatic, excessively emotional, confrontational, erratic, and impulsive in their behaviors.¹ They often have comorbid mood and anxiety disorders, as well as a disproportionately high co-occurrence of functional disorders.^3,7 Their rates of health care utilization can be substantial. Because individuals with one of these PDs sometimes exhibit reckless and impulsive behavior, physicians should be aware these patients have a high risk of physical injuries (fights, accidents, self-injurious behavior), suicide attempts, risky sexual behaviors, and unplanned pregnancy.^8,9

CASE 2 › Sheryl B is a 34-year-old new patient with a history of irritable bowel syndrome, fibromyalgia, depression, and anxiety who shows up for her appointment an hour late. She is upset and blames the office scheduler for not reminding her of the appointment. She brings a list of medications from her previous physician that includes sertraline, clonazepam, gabapentin, oxycodone, and as-needed alprazolam. She insists that her physician increase the dose of the benzodiazepines.

A review of her medical history reveals diagnoses of anxiety, bipolar disorder, and posttraumatic stress disorder. Ms. B has also engaged in superficial cutting since adolescence, often triggered by arguments with her boyfriend. Currently, she attributes her anxiety and pain to not receiving the “correct medications” because of her transition from a previous physician who “knew her better than any other doctor.” After the FP explains to Ms. B that he would have to carefully review her case before continuing to prescribe benzodiazepines, she becomes tearful and argumentative, proclaiming, “You won’t give me the only thing that will help me because you want me to be miserable!”

Ms. B exhibits many cluster B personality traits consistent with borderline PD. How should the FP respond to her claims? (For the answer, click here.)

Borderline PD is the most studied of the PDs. It can be a stigmatizing diagnosis, and even experienced psychiatrists may hesitate to inform patients of this diagnosis.¹⁰ Patients with borderline PD may be erroneously diagnosed with bipolar disorder, treatment-resistant depression, or posttraumatic stress disorder because of a complicated clinical presentation, physician unfamiliarity with diagnostic criteria, or the presence of genuine comorbid conditions.^3,11

The etiology of this disorder appears to be multifactorial, and includes genetic predisposition, disruptive parent-child relationships (especially separation), and, often, past sexual or physical trauma.^9,12

Predominant clinical features include emotional lability, efforts to avoid abandonment, extremes of idealization and devaluation, unstable and intense interpersonal relationships, and impulsivity.¹ Characteristically, these patients also engage in self-injurious behaviors.^13,14 Common defense mechanisms used by patients with borderline PD include splitting (viewing others as either all good or all bad), acting out (yelling, agitation, or violence), and passive aggression (TABLE 1^3,4).

Cluster C: Anxious, fearful

Individuals with cluster C PDs appear anxious, fearful, and worried. They have features that overlap with anxiety disorders.¹⁵

CASE 3 › Judy C is a 40-year-old lawyer with a history of gastroesophageal reflux disorder, hypertension, and anxiety who presents for a 3-week follow-up visit after starting sertraline. The patient describes herself as a perfectionist who has increased work-related stress recently because she has to “do extra work for my colleagues who don’t know how to get things done right.” She recently fired her assistant for “not understanding my filing system.” She appears formal and serious, often looking at her watch during the evaluation.

Ms. C demonstrates a pattern of perfectionism, formality, and rigidity in thought and behavior characteristic of obsessive-compulsive PD. What treatment should her physician recommend? (For the answer, click here.)

Unlike patients with frank delusions, patients with schizotypal personality disorder are willing to consider alternative explanations for their odd beliefs.

Obsessive-compulsive PD. Although this disorder is associated with significant anxiety, patients often view the specific traits of obsessive-compulsive PD, such as perfectionism, as desirable. Neurotic defense mechanisms are common, especially rationalization, intellectualization, and isolation of affect (TABLE 2^3,4). These patients appear formal, rigid, and serious, and are preoccupied with rules and orderliness to achieve perfection.¹ Significant anxiety often arises from fear of making mistakes and ruminating on decision-making.^1,11,15

Although some overlap exists between obsessive-compulsive disorder (OCD) and obsessive-compulsive PD, patients with OCD exhibit distinct obsessions and associated compulsive behavior, whereas those with obsessive-compulsive PD do not.¹

In terms of treatment, it is generally appropriate to recognize the 2 conditions as distinct entities.¹⁵ OCD responds well to cognitive behavioral therapies and high-dose selective serotonin reuptake inhibitors (SSRIs).¹⁶ In contrast, there is little data that suggests antidepressants are effective for obsessive-compulsive PD, and treatment is aimed at addressing comorbid anxiety with psychotherapy and pharmacotherapy, if needed.^11,15

Continue to psychotherapy for PD is the first-line treatment >>

Psychotherapy for PD is the first-line treatment

Psychotherapy is the most effective treatment for PDs.^11,17,18 Several psychotherapies are used to treat these disorders, including dialectical behavioral therapy, schema therapy, and cognitive behavioral therapy (CBT). A recent study demonstrated the superiority of several evidence-based psychotherapies for PD compared to treatment-as-usual.¹⁷ Even more promising is that certain benefits have been demonstrated when psychotherapy is provided by clinicians without advanced mental health training.^19-21 However, the benefits of therapies for specific disorders are often limited by lack of available data, patient preference, and accessibility of resources.

Limited evidence supports pharmacotherapy

The use of pharmacotherapy for treating PDs is common, although there’s limited evidence to support the practice.^11,22 Certain circumstances may allow for the judicious use of medication, although prescribing strategies are based largely on clinical experience and expert opinion.

Prescribers should emphasize a realistic perspective on treatment response, because research suggests at best a mild-moderate response of some personality traits to pharmacotherapy.^11,22-25 There is no evidence for polypharmacy in treating PDs, and FPs should allow for sufficient treatment duration, switch medications rather than augment ineffective treatments, and resist the urge to prescribe for every psychological crisis.^11,22,25,26

Patient safety should always be a consideration when prescribing medication. Because use of second-generation antipsychotics is associated with the metabolic syndrome, the patient’s baseline weight and fasting glucose, lipids, and hemoglobin A1c levels should be obtained and monitored regularly. Weight gain can be particularly distressing to patients, increase stress and anxiety, and hinder the doctor-patient relationship.²⁵ Finally, medications with abuse potential or that can be lethal in overdose (eg, tricyclic antidepressants and benzodiazepines) are best avoided in patients with emotional lability and impulsivity.^25,26

Tailor treatment to the specific PD

Patients often view the specific traits of obsessive-compulsive personality disorder, such as perfectionism, as desirable.

Tx for cluster A disorders. Few studies have examined the effectiveness of psychotherapies for cluster A disorders. Cognitive therapy may have benefit in addressing cognitive distortions and social impairment in schizotypal PD.^11,12,22 There is little evidence supporting psychotherapy for paranoid PD, because challenging patients’ beliefs in this form is likely to exacerbate paranoia. Low-dose risperidone has demonstrated some beneficial effects on perceptual disturbances; however, the adverse metabolic effects of this medication may outweigh any potential benefit, as these symptoms are often not distressing to patients.^6,27 In comparison, patients often find deficits in memory and attention to be more bothersome, and some data suggest that the alpha-2 agonist guanfacine may help treat these symptoms.²⁸

Tx for cluster B disorders. Several forms of psychotherapy have proven effective in managing symptoms and improving overall functioning in patients with borderline PD, including dialectical behavioral therapy, mentalization-based therapy, transference-focused therapy, and schema therapy.²⁹ Dialectical behavioral therapy is often the initial treatment because it emphasizes reducing self-harm behaviors and emotion regulation.^11,17,26

Gunderson¹⁹ developed a more basic approach to treating borderline PD that is intended to be used by all clinicians who treat the disorder, and not just mental health professionals with advanced training in psychotherapy. A large, multisite randomized controlled trial found that the clinical efficacy of the technique, known as good psychiatric management, rivaled that of dialectical behavioral therapy.^20,21

The general premise is that clinicians foster a therapeutic relationship that is supportive, engaging, and flexible. Physicians are encouraged to educate patients about the disorder and emphasize improvement in daily functioning. Clinicians should share the diagnosis with patients, which may give patients a sense of relief in having an accurate diagnosis and allow them to fully invest in diagnosis-specific treatments.¹⁹

Systematic reviews and meta-analyses of studies that evaluated pharmacotherapy for borderline PD often have had conflicting conclusions as a result of analyzing data from underpowered studies with varying study designs.^{23,24,26,30,31} In targeting specific symptoms of the disorder, the most consistent evidence has supported the use of antipsychotics for cognitive perceptual disturbances; patients commonly experience depersonalization or out-of-body experiences.²⁵ Additionally, the use of antipsychotics and mood stabilizers (lamotrigine and topiramate) appears to be somewhat effective for managing emotional lability and impulsivity.^26,32,33 Despite the widespread use of SSRIs, a recent systematic review found the least support for these and other antidepressants for management of borderline PD.²⁵

Tx for cluster C disorders. Some evidence supports using cognitive and interpersonal psychotherapies to treat cluster C PDs.³⁴ In contrast, there is little evidence to support the use of pharmacotherapy.³⁵ However, given the significant overlap among these disorders (especially avoidant PD) and social phobia and generalized anxiety disorder, effective pharmacologic strategies can be inferred based on data for those conditions.¹¹ SSRIs, serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), and gabapentin have demonstrated efficacy in anxiety disorders and are reasonable and safe initial treatments for patients with a cluster C PD.^11,34

Continue for the answers >>

CASE 1 › Mr. A’s schizotypal PD symptoms interfere with medication adherence because of his unusual belief system. Importantly, unlike patients with frank delusions, patients with schizotypal PD are willing to consider alternative explanations for their unusual beliefs. Mr. A’s intense suspiciousness may indicate some degree of overlap between paranoid and schizotypal PDs.

The FP is patient and willing to listen to Mr. A’s beliefs without devaluing them. To improve medication adherence, the FP offers him reasonable alternatives with clear explanations. (“I understand you have concerns about previous medications. At the same time, it seems that managing your blood pressure and cholesterol is important to you. Can we discuss alternative treatments?”)

CASE 2 › In response to Ms. B’s borderline PD, the FP must be cautious to avoid reacting out of frustration, which may upset the patient and validate her mistrust. The FP first reflects her anger (“I can tell you are upset because you don’t think I want to help you”), which may allow her to calmly engage in a discussion. He wants to recognize Ms. B’s dramatic behavior, but not reward it with added attention and unreasonable concessions. To help establish rapport, he provides a statement to legitimize Ms. B’s concerns (“Many patients would be frustrated during the process of changing physicians”).

The FP listens empathically to Ms. B, sets clear limits, and provides consistent and evidence-based treatments. He also provides early referral to psychotherapy, but to mitigate any perceived abandonment, he assures Ms. B he will remain involved with her treatment. (“It sounds like managing your anxiety is important to you, and often psychiatrists or therapists can help give additional options for treatment. I want you to know that I am still your doctor and we can review their recommendations together at our next visit.”)

Psychotherapy can be beneficial for patients with personality disorders, even when it is provided by clinicians without advanced mental health training.

CASE 3 › The FP recognizes that Ms. C’s pattern of perfectionism, formality, and rigidity in thought and behavior are likely a manifestation of obsessive-compulsive PD, and that the maladaptive psychological traits underlying her anxiety are distinct from a primary anxiety disorder.

An SSRI may be a reasonable option to treat Ms. B’s anxiety, and the FP also refers her for CBT. (“I can tell you are feeling really anxious and many people feel that way, especially with work. I think the medication is a good start, but I wonder if we could discuss other forms of therapy to maximize your symptom improvement.”) Because of their exacting nature, many patients with cluster C personality traits are willing to engage in treatments, especially if they are supported by data and recommended by a knowledgeable physician.

CORRESPONDENCE
Nicholas Morcos, Department of Psychiatry, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109; [email protected].

Personality disorders (PDs) are common, affecting up to 15% of US adults, and are associated with comorbid medical and psychiatric conditions and increased utilization of health care resources.^1,2 Having a basic understanding of these patterns of thinking and behaving can help family physicians (FPs) identify specific PD diagnoses, ensure appropriate treatment, and reduce the frustration that arises when an individual is viewed as a “difficult patient.”

Here we describe the diagnostic features of the disorders in the 3 major clusters of PDs and review an effective approach to the management of the most common disorder in each cluster, using a case study patient.

Defense mechanisms offer clues that your patient may have a PD

Personality is an enduring pattern of inner experience and behaviors that is relatively stable across time and in different situations. Such traits comprise an individual’s inherent makeup.¹ PDs are diagnosed when an individual’s personality traits create significant distress or impairment in daily functioning. Specifically, PDs have a negative impact on cognition, affect, interpersonal relationships, and/or impulse control.¹

One of the ways people alleviate distress is by using defense mechanisms. Defense mechanisms are unconscious mental processes that individuals use to resolve conflicts, and thereby reduce anxiety and depression on a conscious level. Taken alone, defense mechanisms are not pathologic, but they may become maladaptive in certain stressful circumstances, such as when receiving medical treatment. Recognizing patterns of chronic use of certain defense mechanisms may be a clue that your patient has a PD. TABLE 1^3,4 and TABLE 2^3,4 provide an overview of common defense mechanisms used by patients with PDs.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) organizes PDs into 3 clusters based on similar and often overlapping symptoms.¹TABLE 3¹ provides a brief summary of the characteristic features of each disorder in these clusters.

Cluster A: Odd, eccentric

Patients with one of these disorders are odd, eccentric, or bizarre in their behavior and thinking. There appears to be a genetic link between cluster A PDs (especially schizotypal) and schizophrenia.⁵ These patients rarely seek treatment for their disorder because they have limited insight into their maladaptive traits.^5,6

CASE 1 › Daniel A, age 57, has hypertension and hyperlipidemia and comes in to see his FP for a 6-month follow-up appointment. He never misses appointments, but has a history of poor adherence with prescribed medications. He enjoys his discussions with you in the office, although he often perseverates on conspiracy theories. He lives alone and has never been married. He believes that some of the previously prescribed medications, including a statin and a thiazide diuretic, were interfering with the absorption of “positive nutrients” in his diet. He also refuses to take the generic form of a statin, which he believes was adulterated by the government to be sold at lower cost.

Mr. A demonstrates the odd and eccentric beliefs that characterize schizotypal personality disorder. How can his FP best help him adhere to his medication regimen? (For the answer, click here.)

Schizotypal personality disorder shares certain disturbances of thought with schizophrenia, and is believed to exist on a spectrum with other primary psychotic disorders. Support for this theory comes from the higher rates of schizotypal PD among family members of patients with schizophrenia. There is a genetic component to the disorder.^3,5,6

Clinically, these patients appear odd and eccentric with unusual beliefs. They may have a fascination with magic, clairvoyance, telepathy, or other such notions.^1,5 Although the perceptual disturbances are unusual and often bizarre, they are not frank delusions: patients with schizotypal PD are willing to consider alternative explanations for their beliefs and can engage in rational discussion. Cognitive deficits, particularly of memory and attention, are common and distressing to patients. Frequently, the presenting complaint is depression and anxiety due to the emotional discord and isolation from others.^1,3,5,6

Continue to cluster B >>

Cluster B: Dramatic, erratic

Does your patient complain that you don't understand him "the way his other doctor did"? Or does he frequently lose his temper? Perhaps it's time to consider a personality disorder.

Patients with cluster B PDs are dramatic, excessively emotional, confrontational, erratic, and impulsive in their behaviors.¹ They often have comorbid mood and anxiety disorders, as well as a disproportionately high co-occurrence of functional disorders.^3,7 Their rates of health care utilization can be substantial. Because individuals with one of these PDs sometimes exhibit reckless and impulsive behavior, physicians should be aware these patients have a high risk of physical injuries (fights, accidents, self-injurious behavior), suicide attempts, risky sexual behaviors, and unplanned pregnancy.^8,9

CASE 2 › Sheryl B is a 34-year-old new patient with a history of irritable bowel syndrome, fibromyalgia, depression, and anxiety who shows up for her appointment an hour late. She is upset and blames the office scheduler for not reminding her of the appointment. She brings a list of medications from her previous physician that includes sertraline, clonazepam, gabapentin, oxycodone, and as-needed alprazolam. She insists that her physician increase the dose of the benzodiazepines.

A review of her medical history reveals diagnoses of anxiety, bipolar disorder, and posttraumatic stress disorder. Ms. B has also engaged in superficial cutting since adolescence, often triggered by arguments with her boyfriend. Currently, she attributes her anxiety and pain to not receiving the “correct medications” because of her transition from a previous physician who “knew her better than any other doctor.” After the FP explains to Ms. B that he would have to carefully review her case before continuing to prescribe benzodiazepines, she becomes tearful and argumentative, proclaiming, “You won’t give me the only thing that will help me because you want me to be miserable!”

Ms. B exhibits many cluster B personality traits consistent with borderline PD. How should the FP respond to her claims? (For the answer, click here.)

Borderline PD is the most studied of the PDs. It can be a stigmatizing diagnosis, and even experienced psychiatrists may hesitate to inform patients of this diagnosis.¹⁰ Patients with borderline PD may be erroneously diagnosed with bipolar disorder, treatment-resistant depression, or posttraumatic stress disorder because of a complicated clinical presentation, physician unfamiliarity with diagnostic criteria, or the presence of genuine comorbid conditions.^3,11

The etiology of this disorder appears to be multifactorial, and includes genetic predisposition, disruptive parent-child relationships (especially separation), and, often, past sexual or physical trauma.^9,12

Predominant clinical features include emotional lability, efforts to avoid abandonment, extremes of idealization and devaluation, unstable and intense interpersonal relationships, and impulsivity.¹ Characteristically, these patients also engage in self-injurious behaviors.^13,14 Common defense mechanisms used by patients with borderline PD include splitting (viewing others as either all good or all bad), acting out (yelling, agitation, or violence), and passive aggression (TABLE 1^3,4).

Cluster C: Anxious, fearful

Individuals with cluster C PDs appear anxious, fearful, and worried. They have features that overlap with anxiety disorders.¹⁵

CASE 3 › Judy C is a 40-year-old lawyer with a history of gastroesophageal reflux disorder, hypertension, and anxiety who presents for a 3-week follow-up visit after starting sertraline. The patient describes herself as a perfectionist who has increased work-related stress recently because she has to “do extra work for my colleagues who don’t know how to get things done right.” She recently fired her assistant for “not understanding my filing system.” She appears formal and serious, often looking at her watch during the evaluation.

Ms. C demonstrates a pattern of perfectionism, formality, and rigidity in thought and behavior characteristic of obsessive-compulsive PD. What treatment should her physician recommend? (For the answer, click here.)

Unlike patients with frank delusions, patients with schizotypal personality disorder are willing to consider alternative explanations for their odd beliefs.

Obsessive-compulsive PD. Although this disorder is associated with significant anxiety, patients often view the specific traits of obsessive-compulsive PD, such as perfectionism, as desirable. Neurotic defense mechanisms are common, especially rationalization, intellectualization, and isolation of affect (TABLE 2^3,4). These patients appear formal, rigid, and serious, and are preoccupied with rules and orderliness to achieve perfection.¹ Significant anxiety often arises from fear of making mistakes and ruminating on decision-making.^1,11,15

Although some overlap exists between obsessive-compulsive disorder (OCD) and obsessive-compulsive PD, patients with OCD exhibit distinct obsessions and associated compulsive behavior, whereas those with obsessive-compulsive PD do not.¹

In terms of treatment, it is generally appropriate to recognize the 2 conditions as distinct entities.¹⁵ OCD responds well to cognitive behavioral therapies and high-dose selective serotonin reuptake inhibitors (SSRIs).¹⁶ In contrast, there is little data that suggests antidepressants are effective for obsessive-compulsive PD, and treatment is aimed at addressing comorbid anxiety with psychotherapy and pharmacotherapy, if needed.^11,15

Continue to psychotherapy for PD is the first-line treatment >>

Psychotherapy for PD is the first-line treatment

Psychotherapy is the most effective treatment for PDs.^11,17,18 Several psychotherapies are used to treat these disorders, including dialectical behavioral therapy, schema therapy, and cognitive behavioral therapy (CBT). A recent study demonstrated the superiority of several evidence-based psychotherapies for PD compared to treatment-as-usual.¹⁷ Even more promising is that certain benefits have been demonstrated when psychotherapy is provided by clinicians without advanced mental health training.^19-21 However, the benefits of therapies for specific disorders are often limited by lack of available data, patient preference, and accessibility of resources.

Limited evidence supports pharmacotherapy

The use of pharmacotherapy for treating PDs is common, although there’s limited evidence to support the practice.^11,22 Certain circumstances may allow for the judicious use of medication, although prescribing strategies are based largely on clinical experience and expert opinion.

Prescribers should emphasize a realistic perspective on treatment response, because research suggests at best a mild-moderate response of some personality traits to pharmacotherapy.^11,22-25 There is no evidence for polypharmacy in treating PDs, and FPs should allow for sufficient treatment duration, switch medications rather than augment ineffective treatments, and resist the urge to prescribe for every psychological crisis.^11,22,25,26

Patient safety should always be a consideration when prescribing medication. Because use of second-generation antipsychotics is associated with the metabolic syndrome, the patient’s baseline weight and fasting glucose, lipids, and hemoglobin A1c levels should be obtained and monitored regularly. Weight gain can be particularly distressing to patients, increase stress and anxiety, and hinder the doctor-patient relationship.²⁵ Finally, medications with abuse potential or that can be lethal in overdose (eg, tricyclic antidepressants and benzodiazepines) are best avoided in patients with emotional lability and impulsivity.^25,26

Tailor treatment to the specific PD

Patients often view the specific traits of obsessive-compulsive personality disorder, such as perfectionism, as desirable.

Tx for cluster A disorders. Few studies have examined the effectiveness of psychotherapies for cluster A disorders. Cognitive therapy may have benefit in addressing cognitive distortions and social impairment in schizotypal PD.^11,12,22 There is little evidence supporting psychotherapy for paranoid PD, because challenging patients’ beliefs in this form is likely to exacerbate paranoia. Low-dose risperidone has demonstrated some beneficial effects on perceptual disturbances; however, the adverse metabolic effects of this medication may outweigh any potential benefit, as these symptoms are often not distressing to patients.^6,27 In comparison, patients often find deficits in memory and attention to be more bothersome, and some data suggest that the alpha-2 agonist guanfacine may help treat these symptoms.²⁸

Tx for cluster B disorders. Several forms of psychotherapy have proven effective in managing symptoms and improving overall functioning in patients with borderline PD, including dialectical behavioral therapy, mentalization-based therapy, transference-focused therapy, and schema therapy.²⁹ Dialectical behavioral therapy is often the initial treatment because it emphasizes reducing self-harm behaviors and emotion regulation.^11,17,26

Gunderson¹⁹ developed a more basic approach to treating borderline PD that is intended to be used by all clinicians who treat the disorder, and not just mental health professionals with advanced training in psychotherapy. A large, multisite randomized controlled trial found that the clinical efficacy of the technique, known as good psychiatric management, rivaled that of dialectical behavioral therapy.^20,21

The general premise is that clinicians foster a therapeutic relationship that is supportive, engaging, and flexible. Physicians are encouraged to educate patients about the disorder and emphasize improvement in daily functioning. Clinicians should share the diagnosis with patients, which may give patients a sense of relief in having an accurate diagnosis and allow them to fully invest in diagnosis-specific treatments.¹⁹

Systematic reviews and meta-analyses of studies that evaluated pharmacotherapy for borderline PD often have had conflicting conclusions as a result of analyzing data from underpowered studies with varying study designs.^{23,24,26,30,31} In targeting specific symptoms of the disorder, the most consistent evidence has supported the use of antipsychotics for cognitive perceptual disturbances; patients commonly experience depersonalization or out-of-body experiences.²⁵ Additionally, the use of antipsychotics and mood stabilizers (lamotrigine and topiramate) appears to be somewhat effective for managing emotional lability and impulsivity.^26,32,33 Despite the widespread use of SSRIs, a recent systematic review found the least support for these and other antidepressants for management of borderline PD.²⁵

Tx for cluster C disorders. Some evidence supports using cognitive and interpersonal psychotherapies to treat cluster C PDs.³⁴ In contrast, there is little evidence to support the use of pharmacotherapy.³⁵ However, given the significant overlap among these disorders (especially avoidant PD) and social phobia and generalized anxiety disorder, effective pharmacologic strategies can be inferred based on data for those conditions.¹¹ SSRIs, serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), and gabapentin have demonstrated efficacy in anxiety disorders and are reasonable and safe initial treatments for patients with a cluster C PD.^11,34

Continue for the answers >>

CASE 1 › Mr. A’s schizotypal PD symptoms interfere with medication adherence because of his unusual belief system. Importantly, unlike patients with frank delusions, patients with schizotypal PD are willing to consider alternative explanations for their unusual beliefs. Mr. A’s intense suspiciousness may indicate some degree of overlap between paranoid and schizotypal PDs.

The FP is patient and willing to listen to Mr. A’s beliefs without devaluing them. To improve medication adherence, the FP offers him reasonable alternatives with clear explanations. (“I understand you have concerns about previous medications. At the same time, it seems that managing your blood pressure and cholesterol is important to you. Can we discuss alternative treatments?”)

CASE 2 › In response to Ms. B’s borderline PD, the FP must be cautious to avoid reacting out of frustration, which may upset the patient and validate her mistrust. The FP first reflects her anger (“I can tell you are upset because you don’t think I want to help you”), which may allow her to calmly engage in a discussion. He wants to recognize Ms. B’s dramatic behavior, but not reward it with added attention and unreasonable concessions. To help establish rapport, he provides a statement to legitimize Ms. B’s concerns (“Many patients would be frustrated during the process of changing physicians”).

The FP listens empathically to Ms. B, sets clear limits, and provides consistent and evidence-based treatments. He also provides early referral to psychotherapy, but to mitigate any perceived abandonment, he assures Ms. B he will remain involved with her treatment. (“It sounds like managing your anxiety is important to you, and often psychiatrists or therapists can help give additional options for treatment. I want you to know that I am still your doctor and we can review their recommendations together at our next visit.”)

Psychotherapy can be beneficial for patients with personality disorders, even when it is provided by clinicians without advanced mental health training.

CASE 3 › The FP recognizes that Ms. C’s pattern of perfectionism, formality, and rigidity in thought and behavior are likely a manifestation of obsessive-compulsive PD, and that the maladaptive psychological traits underlying her anxiety are distinct from a primary anxiety disorder.

An SSRI may be a reasonable option to treat Ms. B’s anxiety, and the FP also refers her for CBT. (“I can tell you are feeling really anxious and many people feel that way, especially with work. I think the medication is a good start, but I wonder if we could discuss other forms of therapy to maximize your symptom improvement.”) Because of their exacting nature, many patients with cluster C personality traits are willing to engage in treatments, especially if they are supported by data and recommended by a knowledgeable physician.

CORRESPONDENCE
Nicholas Morcos, Department of Psychiatry, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109; [email protected].

Personality disorders (PDs) are common, affecting up to 15% of US adults, and are associated with comorbid medical and psychiatric conditions and increased utilization of health care resources.^1,2 Having a basic understanding of these patterns of thinking and behaving can help family physicians (FPs) identify specific PD diagnoses, ensure appropriate treatment, and reduce the frustration that arises when an individual is viewed as a “difficult patient.”

Here we describe the diagnostic features of the disorders in the 3 major clusters of PDs and review an effective approach to the management of the most common disorder in each cluster, using a case study patient.

Defense mechanisms offer clues that your patient may have a PD

Personality is an enduring pattern of inner experience and behaviors that is relatively stable across time and in different situations. Such traits comprise an individual’s inherent makeup.¹ PDs are diagnosed when an individual’s personality traits create significant distress or impairment in daily functioning. Specifically, PDs have a negative impact on cognition, affect, interpersonal relationships, and/or impulse control.¹

One of the ways people alleviate distress is by using defense mechanisms. Defense mechanisms are unconscious mental processes that individuals use to resolve conflicts, and thereby reduce anxiety and depression on a conscious level. Taken alone, defense mechanisms are not pathologic, but they may become maladaptive in certain stressful circumstances, such as when receiving medical treatment. Recognizing patterns of chronic use of certain defense mechanisms may be a clue that your patient has a PD. TABLE 1^3,4 and TABLE 2^3,4 provide an overview of common defense mechanisms used by patients with PDs.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) organizes PDs into 3 clusters based on similar and often overlapping symptoms.¹TABLE 3¹ provides a brief summary of the characteristic features of each disorder in these clusters.

Cluster A: Odd, eccentric

Patients with one of these disorders are odd, eccentric, or bizarre in their behavior and thinking. There appears to be a genetic link between cluster A PDs (especially schizotypal) and schizophrenia.⁵ These patients rarely seek treatment for their disorder because they have limited insight into their maladaptive traits.^5,6

CASE 1 › Daniel A, age 57, has hypertension and hyperlipidemia and comes in to see his FP for a 6-month follow-up appointment. He never misses appointments, but has a history of poor adherence with prescribed medications. He enjoys his discussions with you in the office, although he often perseverates on conspiracy theories. He lives alone and has never been married. He believes that some of the previously prescribed medications, including a statin and a thiazide diuretic, were interfering with the absorption of “positive nutrients” in his diet. He also refuses to take the generic form of a statin, which he believes was adulterated by the government to be sold at lower cost.

Mr. A demonstrates the odd and eccentric beliefs that characterize schizotypal personality disorder. How can his FP best help him adhere to his medication regimen? (For the answer, click here.)

Schizotypal personality disorder shares certain disturbances of thought with schizophrenia, and is believed to exist on a spectrum with other primary psychotic disorders. Support for this theory comes from the higher rates of schizotypal PD among family members of patients with schizophrenia. There is a genetic component to the disorder.^3,5,6

Clinically, these patients appear odd and eccentric with unusual beliefs. They may have a fascination with magic, clairvoyance, telepathy, or other such notions.^1,5 Although the perceptual disturbances are unusual and often bizarre, they are not frank delusions: patients with schizotypal PD are willing to consider alternative explanations for their beliefs and can engage in rational discussion. Cognitive deficits, particularly of memory and attention, are common and distressing to patients. Frequently, the presenting complaint is depression and anxiety due to the emotional discord and isolation from others.^1,3,5,6

Continue to cluster B >>

Cluster B: Dramatic, erratic

Does your patient complain that you don't understand him "the way his other doctor did"? Or does he frequently lose his temper? Perhaps it's time to consider a personality disorder.

Patients with cluster B PDs are dramatic, excessively emotional, confrontational, erratic, and impulsive in their behaviors.¹ They often have comorbid mood and anxiety disorders, as well as a disproportionately high co-occurrence of functional disorders.^3,7 Their rates of health care utilization can be substantial. Because individuals with one of these PDs sometimes exhibit reckless and impulsive behavior, physicians should be aware these patients have a high risk of physical injuries (fights, accidents, self-injurious behavior), suicide attempts, risky sexual behaviors, and unplanned pregnancy.^8,9

CASE 2 › Sheryl B is a 34-year-old new patient with a history of irritable bowel syndrome, fibromyalgia, depression, and anxiety who shows up for her appointment an hour late. She is upset and blames the office scheduler for not reminding her of the appointment. She brings a list of medications from her previous physician that includes sertraline, clonazepam, gabapentin, oxycodone, and as-needed alprazolam. She insists that her physician increase the dose of the benzodiazepines.

A review of her medical history reveals diagnoses of anxiety, bipolar disorder, and posttraumatic stress disorder. Ms. B has also engaged in superficial cutting since adolescence, often triggered by arguments with her boyfriend. Currently, she attributes her anxiety and pain to not receiving the “correct medications” because of her transition from a previous physician who “knew her better than any other doctor.” After the FP explains to Ms. B that he would have to carefully review her case before continuing to prescribe benzodiazepines, she becomes tearful and argumentative, proclaiming, “You won’t give me the only thing that will help me because you want me to be miserable!”

Ms. B exhibits many cluster B personality traits consistent with borderline PD. How should the FP respond to her claims? (For the answer, click here.)

Borderline PD is the most studied of the PDs. It can be a stigmatizing diagnosis, and even experienced psychiatrists may hesitate to inform patients of this diagnosis.¹⁰ Patients with borderline PD may be erroneously diagnosed with bipolar disorder, treatment-resistant depression, or posttraumatic stress disorder because of a complicated clinical presentation, physician unfamiliarity with diagnostic criteria, or the presence of genuine comorbid conditions.^3,11

The etiology of this disorder appears to be multifactorial, and includes genetic predisposition, disruptive parent-child relationships (especially separation), and, often, past sexual or physical trauma.^9,12

Predominant clinical features include emotional lability, efforts to avoid abandonment, extremes of idealization and devaluation, unstable and intense interpersonal relationships, and impulsivity.¹ Characteristically, these patients also engage in self-injurious behaviors.^13,14 Common defense mechanisms used by patients with borderline PD include splitting (viewing others as either all good or all bad), acting out (yelling, agitation, or violence), and passive aggression (TABLE 1^3,4).

Cluster C: Anxious, fearful

Individuals with cluster C PDs appear anxious, fearful, and worried. They have features that overlap with anxiety disorders.¹⁵

CASE 3 › Judy C is a 40-year-old lawyer with a history of gastroesophageal reflux disorder, hypertension, and anxiety who presents for a 3-week follow-up visit after starting sertraline. The patient describes herself as a perfectionist who has increased work-related stress recently because she has to “do extra work for my colleagues who don’t know how to get things done right.” She recently fired her assistant for “not understanding my filing system.” She appears formal and serious, often looking at her watch during the evaluation.

Ms. C demonstrates a pattern of perfectionism, formality, and rigidity in thought and behavior characteristic of obsessive-compulsive PD. What treatment should her physician recommend? (For the answer, click here.)

Unlike patients with frank delusions, patients with schizotypal personality disorder are willing to consider alternative explanations for their odd beliefs.

Obsessive-compulsive PD. Although this disorder is associated with significant anxiety, patients often view the specific traits of obsessive-compulsive PD, such as perfectionism, as desirable. Neurotic defense mechanisms are common, especially rationalization, intellectualization, and isolation of affect (TABLE 2^3,4). These patients appear formal, rigid, and serious, and are preoccupied with rules and orderliness to achieve perfection.¹ Significant anxiety often arises from fear of making mistakes and ruminating on decision-making.^1,11,15

Although some overlap exists between obsessive-compulsive disorder (OCD) and obsessive-compulsive PD, patients with OCD exhibit distinct obsessions and associated compulsive behavior, whereas those with obsessive-compulsive PD do not.¹

In terms of treatment, it is generally appropriate to recognize the 2 conditions as distinct entities.¹⁵ OCD responds well to cognitive behavioral therapies and high-dose selective serotonin reuptake inhibitors (SSRIs).¹⁶ In contrast, there is little data that suggests antidepressants are effective for obsessive-compulsive PD, and treatment is aimed at addressing comorbid anxiety with psychotherapy and pharmacotherapy, if needed.^11,15

Continue to psychotherapy for PD is the first-line treatment >>

Psychotherapy for PD is the first-line treatment

Psychotherapy is the most effective treatment for PDs.^11,17,18 Several psychotherapies are used to treat these disorders, including dialectical behavioral therapy, schema therapy, and cognitive behavioral therapy (CBT). A recent study demonstrated the superiority of several evidence-based psychotherapies for PD compared to treatment-as-usual.¹⁷ Even more promising is that certain benefits have been demonstrated when psychotherapy is provided by clinicians without advanced mental health training.^19-21 However, the benefits of therapies for specific disorders are often limited by lack of available data, patient preference, and accessibility of resources.

Limited evidence supports pharmacotherapy

The use of pharmacotherapy for treating PDs is common, although there’s limited evidence to support the practice.^11,22 Certain circumstances may allow for the judicious use of medication, although prescribing strategies are based largely on clinical experience and expert opinion.

Prescribers should emphasize a realistic perspective on treatment response, because research suggests at best a mild-moderate response of some personality traits to pharmacotherapy.^11,22-25 There is no evidence for polypharmacy in treating PDs, and FPs should allow for sufficient treatment duration, switch medications rather than augment ineffective treatments, and resist the urge to prescribe for every psychological crisis.^11,22,25,26

Patient safety should always be a consideration when prescribing medication. Because use of second-generation antipsychotics is associated with the metabolic syndrome, the patient’s baseline weight and fasting glucose, lipids, and hemoglobin A1c levels should be obtained and monitored regularly. Weight gain can be particularly distressing to patients, increase stress and anxiety, and hinder the doctor-patient relationship.²⁵ Finally, medications with abuse potential or that can be lethal in overdose (eg, tricyclic antidepressants and benzodiazepines) are best avoided in patients with emotional lability and impulsivity.^25,26

Tailor treatment to the specific PD

Patients often view the specific traits of obsessive-compulsive personality disorder, such as perfectionism, as desirable.

Tx for cluster A disorders. Few studies have examined the effectiveness of psychotherapies for cluster A disorders. Cognitive therapy may have benefit in addressing cognitive distortions and social impairment in schizotypal PD.^11,12,22 There is little evidence supporting psychotherapy for paranoid PD, because challenging patients’ beliefs in this form is likely to exacerbate paranoia. Low-dose risperidone has demonstrated some beneficial effects on perceptual disturbances; however, the adverse metabolic effects of this medication may outweigh any potential benefit, as these symptoms are often not distressing to patients.^6,27 In comparison, patients often find deficits in memory and attention to be more bothersome, and some data suggest that the alpha-2 agonist guanfacine may help treat these symptoms.²⁸

Tx for cluster B disorders. Several forms of psychotherapy have proven effective in managing symptoms and improving overall functioning in patients with borderline PD, including dialectical behavioral therapy, mentalization-based therapy, transference-focused therapy, and schema therapy.²⁹ Dialectical behavioral therapy is often the initial treatment because it emphasizes reducing self-harm behaviors and emotion regulation.^11,17,26

Gunderson¹⁹ developed a more basic approach to treating borderline PD that is intended to be used by all clinicians who treat the disorder, and not just mental health professionals with advanced training in psychotherapy. A large, multisite randomized controlled trial found that the clinical efficacy of the technique, known as good psychiatric management, rivaled that of dialectical behavioral therapy.^20,21

The general premise is that clinicians foster a therapeutic relationship that is supportive, engaging, and flexible. Physicians are encouraged to educate patients about the disorder and emphasize improvement in daily functioning. Clinicians should share the diagnosis with patients, which may give patients a sense of relief in having an accurate diagnosis and allow them to fully invest in diagnosis-specific treatments.¹⁹

Systematic reviews and meta-analyses of studies that evaluated pharmacotherapy for borderline PD often have had conflicting conclusions as a result of analyzing data from underpowered studies with varying study designs.^{23,24,26,30,31} In targeting specific symptoms of the disorder, the most consistent evidence has supported the use of antipsychotics for cognitive perceptual disturbances; patients commonly experience depersonalization or out-of-body experiences.²⁵ Additionally, the use of antipsychotics and mood stabilizers (lamotrigine and topiramate) appears to be somewhat effective for managing emotional lability and impulsivity.^26,32,33 Despite the widespread use of SSRIs, a recent systematic review found the least support for these and other antidepressants for management of borderline PD.²⁵

Tx for cluster C disorders. Some evidence supports using cognitive and interpersonal psychotherapies to treat cluster C PDs.³⁴ In contrast, there is little evidence to support the use of pharmacotherapy.³⁵ However, given the significant overlap among these disorders (especially avoidant PD) and social phobia and generalized anxiety disorder, effective pharmacologic strategies can be inferred based on data for those conditions.¹¹ SSRIs, serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), and gabapentin have demonstrated efficacy in anxiety disorders and are reasonable and safe initial treatments for patients with a cluster C PD.^11,34

Continue for the answers >>

CASE 1 › Mr. A’s schizotypal PD symptoms interfere with medication adherence because of his unusual belief system. Importantly, unlike patients with frank delusions, patients with schizotypal PD are willing to consider alternative explanations for their unusual beliefs. Mr. A’s intense suspiciousness may indicate some degree of overlap between paranoid and schizotypal PDs.

The FP is patient and willing to listen to Mr. A’s beliefs without devaluing them. To improve medication adherence, the FP offers him reasonable alternatives with clear explanations. (“I understand you have concerns about previous medications. At the same time, it seems that managing your blood pressure and cholesterol is important to you. Can we discuss alternative treatments?”)

CASE 2 › In response to Ms. B’s borderline PD, the FP must be cautious to avoid reacting out of frustration, which may upset the patient and validate her mistrust. The FP first reflects her anger (“I can tell you are upset because you don’t think I want to help you”), which may allow her to calmly engage in a discussion. He wants to recognize Ms. B’s dramatic behavior, but not reward it with added attention and unreasonable concessions. To help establish rapport, he provides a statement to legitimize Ms. B’s concerns (“Many patients would be frustrated during the process of changing physicians”).

The FP listens empathically to Ms. B, sets clear limits, and provides consistent and evidence-based treatments. He also provides early referral to psychotherapy, but to mitigate any perceived abandonment, he assures Ms. B he will remain involved with her treatment. (“It sounds like managing your anxiety is important to you, and often psychiatrists or therapists can help give additional options for treatment. I want you to know that I am still your doctor and we can review their recommendations together at our next visit.”)

Psychotherapy can be beneficial for patients with personality disorders, even when it is provided by clinicians without advanced mental health training.

CASE 3 › The FP recognizes that Ms. C’s pattern of perfectionism, formality, and rigidity in thought and behavior are likely a manifestation of obsessive-compulsive PD, and that the maladaptive psychological traits underlying her anxiety are distinct from a primary anxiety disorder.

An SSRI may be a reasonable option to treat Ms. B’s anxiety, and the FP also refers her for CBT. (“I can tell you are feeling really anxious and many people feel that way, especially with work. I think the medication is a good start, but I wonder if we could discuss other forms of therapy to maximize your symptom improvement.”) Because of their exacting nature, many patients with cluster C personality traits are willing to engage in treatments, especially if they are supported by data and recommended by a knowledgeable physician.

CORRESPONDENCE
Nicholas Morcos, Department of Psychiatry, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109; [email protected].

The "Standards of Medical Care in Diabetes" guidelines published in 2015 by the American Diabetes Association (ADA) state that metformin is the preferred initial pharmacotherapy for managing type 2 diabetes.¹ Metformin, a biguanide, enhances insulin sensitivity in muscle and fat tissue and inhibits hepatic glucose production. Advantages of metformin include the longstanding research supporting its efficacy and safety, an expected decrease in the glycated hemoglobin (HbA1c) level of 1% to 1.5%, low cost, minimal hypoglycemic risk, and potential reductions in cardiovascular (CV) events due to decreased low-density lipoprotein (LDL) cholesterol.^1,2

To minimize adverse gastrointestinal effects, start metformin at 500 mg once or twice a day and titrate upward every one to 2 weeks to the target dose.³ To help guide dosing decisions, use the estimated glomerular filtration rate (eGFR) instead of the serum creatinine (SCr) level, because the SCr can translate into a variable range of eGFRs (TABLE 1).^4,5

What if metformin alone isn't enough?

CASE › Richard C, age 50, has type 2 diabetes, hypertension, hyperlipidemia, and obesity. He takes metformin 1 g twice a day for his diabetes. After 3 months on this regimen, his HbA1c is 8.8%. How would you manage Mr. C's diabetes going forward?

If metformin at a maximum tolerated dose does not achieve the HbA1c target after 3 months, add a second oral agent (a sulfonylurea [SU], thiazolidinedione [TZD], dipeptidyl peptidase 4 [DPP-4] inhibitor, or sodium-glucose cotransporter-2 [SGLT2] inhibitor), a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal insulin (TABLE 2).¹

Factors that will affect the choice of the second agent include patient preference, cost, potential adverse effects, impact on weight, efficacy, and risk of hypoglycemia.

Based on cost, familiarity, and longstanding safety data, you decide to give Mr. C an SU, while cautioning him about hypoglycemia.

CASE › Mr. C has now been taking metformin and an SU at maximum doses for 2 years and continues with lifestyle modifications. Though his HbA1c level dropped after adding the SU, over 2 years it has crept up to 8.6% and his mean blood glucose is 186 mg/dL. What are your treatment options now?

If the target HbA1c level is not achieved on dual therapy, consider triple therapy combinations (TABLE 3).¹

In Mr. C's case, a third oral agent could be added, but DPP-4 and SGLT2 are unlikely to get his HbA1c below 7%. TZD may get his HbA1c into the desired range but is associated with adverse effects such as heart failure, edema, and weight gain. Mr. C agrees instead to start a basal insulin in conjunction with metformin. You could continue the SU, but you decide to stop it because the additive effect of these medications increases the risk of hypoglycemia.

CASE › Six months later Mr. C is taking metformin and insulin glargine, a basal insulin, adjusted to a fasting blood glucose of 80 to 130 mg/dL. His HbA1c is still above target at 8.4%, and the mean postprandial blood glucose is 232 mg/dL.

Mr. C is still above target for HbA1c and for postprandial blood glucose (goal: <180 mg/dL), so he needs pharmacotherapy that targets postprandial glucose elevations.¹ His fasting blood glucose readings are at goal, so increasing his insulin glargine is not recommended because it could cause hypoglycemia. An oral agent other than SU could be added, but none is potent enough to lower the HbA1c to goal (TABLE 2).¹ There are 3 other options:

• add a mealtime bolus of insulin
• add a GLP-1 receptor agonist
• switch to premixed (biphasic) insulin.

What to do when basal insulin isn’t enough—with or without oral medsFor type 2 diabetes poorly controlled on basal insulin with or without oral agents, the 2015 ADA treatment guidelines recommend adding a GLP-1 receptor agonist or mealtime insulin.¹ A less desirable alternative is to switch from basal insulin to a twice-daily premixed (biphasic) insulin analog (70/30 aspart mix or 75/25 or 50/50 lispro mix). The human NPH-Regular premixed formulations (70/30) are less costly alternatives. The disadvantage with all premixed insulins is they only cover 2 postprandial glucose elevations a day.^1,6,7

When prescribing medication for T2DM, consider efficacy, cost, tolerability, impact on body weight, comorbidities, risk of hypoglycemia, and patient preference.

Insulin requires multiple daily injections, can lead to weight gain, and carries the risk of hypoglycemia, which causes significant morbidity.^8,9 Daily or weekly administration of a GLP-1 receptor agonist combined with basal insulin can offer a more convenient alternative to mealtime boluses of insulin.

What are GLP-1 receptor agonists?

GLP-1 receptor agonists exert their maximum influence on blood glucose levels during the postprandial period by mimicking the body’s natural incretin hormonal response to oral glucose ingestion.¹⁰ They delay gastric emptying, promote satiety, decrease glucagon secretion, and increase insulin secretion.^10,11 This mechanism blunts the spiking of postprandial blood glucose after a meal and improves blood glucose control and weight reduction.^1,6,7

A systematic review and meta-analysis by Eng and colleagues compared the safety and efficacy of combined GLP-1 agonist and basal insulin with other treatment regimens.⁷ Fifteen randomized controlled trials were included involving 4348 participants with a mean trial duration of 25 weeks.

Compared with all other treatment regimens, the GLP-1 receptor agonist and basal insulin combination not only significantly reduced HbA1c by 0.44% (95% confidence interval [CI], -0.60 to -0.29) and increased the likelihood of attaining an HbA1c of <7.0% (relative risk [RR]=1.92; 95% CI, 1.43 to 2.56) but also reduced weight by 3.22 kg (-4.90 to -1.54) with no increased risk of hypoglycemia (RR=0.99; 0.76 to 1.29).⁷

GLP-1 agonist vs bolus insulin

Compared with basal-bolus insulin regimens, the combination of a GLP-1 receptor agonist with basal insulin has led to a significantly lowered risk of hypoglycemia (RR=0.67; 95% CI, 0.56 to 0.80), greater weight loss (-5.66 kg; 95% CI, -9.8 to -1.51) and an average reduction in HbA1c of 0.1% (95% CI, -0.17 to -0.02).⁷

There are 5 GLP-1 receptor agonists that have US Food and Drug Administration approval for the treatment of type 2 diabetes: albiglutide, dulaglutide, exenatide, exenatide XR, and liraglutide (TABLE 4).^3,12

All 5 agents are administered subcutaneously and packaged in pen-injector form. Adverse effects include nausea, which is transient and diminishes within the first few weeks of therapy, and less commonly, pancreatitis.^3,12

All of the GLP-1 receptor agonists, except short-acting exenatide, carry a warning about the risk of worsening renal function and a possible association with medullary thyroid carcinomas, which were identified in rats, but have not been observed in humans.^3,12 Medications in this drug class have a low risk for precipitating hypoglycemia.¹¹ Cost is their chief disadvantage, although copay reduction cards are available online for most of the products. Evaluate efficacy, ease of use, tolerability, and cost when selecting a GLP-1 receptor agonist.^3,12

CASE › Mr. C prefers a more convenient option than adding another daily injection. Given his obesity, a GLP-1 receptor agonist can help with weight loss and lower his risk for hypoglycemia. To further increase the convenience in dosing, you lean toward either weekly exenatide XR or dulaglutide over basal-bolus combination insulin. Weekly albiglutide is less potent than exenatide XR and dulaglutide in decreasing HbA1c.¹² Mr. C’s insurance plan provides preferred coverage for exenatide XR and he is eligible for a copay savings card, meaning he will pay no more than $25 per month for this new prescription. You prescribe exenatide XR and ask him to record his postprandial blood glucose levels. You follow up in one month to assess his response.

CORRESPONDENCE
Anne Mounsey, MD, University of North Carolina School of Medicine, Department of Family Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599; [email protected].

The "Standards of Medical Care in Diabetes" guidelines published in 2015 by the American Diabetes Association (ADA) state that metformin is the preferred initial pharmacotherapy for managing type 2 diabetes.¹ Metformin, a biguanide, enhances insulin sensitivity in muscle and fat tissue and inhibits hepatic glucose production. Advantages of metformin include the longstanding research supporting its efficacy and safety, an expected decrease in the glycated hemoglobin (HbA1c) level of 1% to 1.5%, low cost, minimal hypoglycemic risk, and potential reductions in cardiovascular (CV) events due to decreased low-density lipoprotein (LDL) cholesterol.^1,2

To minimize adverse gastrointestinal effects, start metformin at 500 mg once or twice a day and titrate upward every one to 2 weeks to the target dose.³ To help guide dosing decisions, use the estimated glomerular filtration rate (eGFR) instead of the serum creatinine (SCr) level, because the SCr can translate into a variable range of eGFRs (TABLE 1).^4,5

What if metformin alone isn't enough?

CASE › Richard C, age 50, has type 2 diabetes, hypertension, hyperlipidemia, and obesity. He takes metformin 1 g twice a day for his diabetes. After 3 months on this regimen, his HbA1c is 8.8%. How would you manage Mr. C's diabetes going forward?

If metformin at a maximum tolerated dose does not achieve the HbA1c target after 3 months, add a second oral agent (a sulfonylurea [SU], thiazolidinedione [TZD], dipeptidyl peptidase 4 [DPP-4] inhibitor, or sodium-glucose cotransporter-2 [SGLT2] inhibitor), a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal insulin (TABLE 2).¹

Factors that will affect the choice of the second agent include patient preference, cost, potential adverse effects, impact on weight, efficacy, and risk of hypoglycemia.

Based on cost, familiarity, and longstanding safety data, you decide to give Mr. C an SU, while cautioning him about hypoglycemia.

CASE › Mr. C has now been taking metformin and an SU at maximum doses for 2 years and continues with lifestyle modifications. Though his HbA1c level dropped after adding the SU, over 2 years it has crept up to 8.6% and his mean blood glucose is 186 mg/dL. What are your treatment options now?

If the target HbA1c level is not achieved on dual therapy, consider triple therapy combinations (TABLE 3).¹

In Mr. C's case, a third oral agent could be added, but DPP-4 and SGLT2 are unlikely to get his HbA1c below 7%. TZD may get his HbA1c into the desired range but is associated with adverse effects such as heart failure, edema, and weight gain. Mr. C agrees instead to start a basal insulin in conjunction with metformin. You could continue the SU, but you decide to stop it because the additive effect of these medications increases the risk of hypoglycemia.

CASE › Six months later Mr. C is taking metformin and insulin glargine, a basal insulin, adjusted to a fasting blood glucose of 80 to 130 mg/dL. His HbA1c is still above target at 8.4%, and the mean postprandial blood glucose is 232 mg/dL.

Mr. C is still above target for HbA1c and for postprandial blood glucose (goal: <180 mg/dL), so he needs pharmacotherapy that targets postprandial glucose elevations.¹ His fasting blood glucose readings are at goal, so increasing his insulin glargine is not recommended because it could cause hypoglycemia. An oral agent other than SU could be added, but none is potent enough to lower the HbA1c to goal (TABLE 2).¹ There are 3 other options:

• add a mealtime bolus of insulin
• add a GLP-1 receptor agonist
• switch to premixed (biphasic) insulin.

What to do when basal insulin isn’t enough—with or without oral medsFor type 2 diabetes poorly controlled on basal insulin with or without oral agents, the 2015 ADA treatment guidelines recommend adding a GLP-1 receptor agonist or mealtime insulin.¹ A less desirable alternative is to switch from basal insulin to a twice-daily premixed (biphasic) insulin analog (70/30 aspart mix or 75/25 or 50/50 lispro mix). The human NPH-Regular premixed formulations (70/30) are less costly alternatives. The disadvantage with all premixed insulins is they only cover 2 postprandial glucose elevations a day.^1,6,7

When prescribing medication for T2DM, consider efficacy, cost, tolerability, impact on body weight, comorbidities, risk of hypoglycemia, and patient preference.

Insulin requires multiple daily injections, can lead to weight gain, and carries the risk of hypoglycemia, which causes significant morbidity.^8,9 Daily or weekly administration of a GLP-1 receptor agonist combined with basal insulin can offer a more convenient alternative to mealtime boluses of insulin.

What are GLP-1 receptor agonists?

GLP-1 receptor agonists exert their maximum influence on blood glucose levels during the postprandial period by mimicking the body’s natural incretin hormonal response to oral glucose ingestion.¹⁰ They delay gastric emptying, promote satiety, decrease glucagon secretion, and increase insulin secretion.^10,11 This mechanism blunts the spiking of postprandial blood glucose after a meal and improves blood glucose control and weight reduction.^1,6,7

A systematic review and meta-analysis by Eng and colleagues compared the safety and efficacy of combined GLP-1 agonist and basal insulin with other treatment regimens.⁷ Fifteen randomized controlled trials were included involving 4348 participants with a mean trial duration of 25 weeks.

Compared with all other treatment regimens, the GLP-1 receptor agonist and basal insulin combination not only significantly reduced HbA1c by 0.44% (95% confidence interval [CI], -0.60 to -0.29) and increased the likelihood of attaining an HbA1c of <7.0% (relative risk [RR]=1.92; 95% CI, 1.43 to 2.56) but also reduced weight by 3.22 kg (-4.90 to -1.54) with no increased risk of hypoglycemia (RR=0.99; 0.76 to 1.29).⁷

GLP-1 agonist vs bolus insulin

Compared with basal-bolus insulin regimens, the combination of a GLP-1 receptor agonist with basal insulin has led to a significantly lowered risk of hypoglycemia (RR=0.67; 95% CI, 0.56 to 0.80), greater weight loss (-5.66 kg; 95% CI, -9.8 to -1.51) and an average reduction in HbA1c of 0.1% (95% CI, -0.17 to -0.02).⁷

There are 5 GLP-1 receptor agonists that have US Food and Drug Administration approval for the treatment of type 2 diabetes: albiglutide, dulaglutide, exenatide, exenatide XR, and liraglutide (TABLE 4).^3,12

All 5 agents are administered subcutaneously and packaged in pen-injector form. Adverse effects include nausea, which is transient and diminishes within the first few weeks of therapy, and less commonly, pancreatitis.^3,12

All of the GLP-1 receptor agonists, except short-acting exenatide, carry a warning about the risk of worsening renal function and a possible association with medullary thyroid carcinomas, which were identified in rats, but have not been observed in humans.^3,12 Medications in this drug class have a low risk for precipitating hypoglycemia.¹¹ Cost is their chief disadvantage, although copay reduction cards are available online for most of the products. Evaluate efficacy, ease of use, tolerability, and cost when selecting a GLP-1 receptor agonist.^3,12

CASE › Mr. C prefers a more convenient option than adding another daily injection. Given his obesity, a GLP-1 receptor agonist can help with weight loss and lower his risk for hypoglycemia. To further increase the convenience in dosing, you lean toward either weekly exenatide XR or dulaglutide over basal-bolus combination insulin. Weekly albiglutide is less potent than exenatide XR and dulaglutide in decreasing HbA1c.¹² Mr. C’s insurance plan provides preferred coverage for exenatide XR and he is eligible for a copay savings card, meaning he will pay no more than $25 per month for this new prescription. You prescribe exenatide XR and ask him to record his postprandial blood glucose levels. You follow up in one month to assess his response.

CORRESPONDENCE
Anne Mounsey, MD, University of North Carolina School of Medicine, Department of Family Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599; [email protected].

The "Standards of Medical Care in Diabetes" guidelines published in 2015 by the American Diabetes Association (ADA) state that metformin is the preferred initial pharmacotherapy for managing type 2 diabetes.¹ Metformin, a biguanide, enhances insulin sensitivity in muscle and fat tissue and inhibits hepatic glucose production. Advantages of metformin include the longstanding research supporting its efficacy and safety, an expected decrease in the glycated hemoglobin (HbA1c) level of 1% to 1.5%, low cost, minimal hypoglycemic risk, and potential reductions in cardiovascular (CV) events due to decreased low-density lipoprotein (LDL) cholesterol.^1,2

To minimize adverse gastrointestinal effects, start metformin at 500 mg once or twice a day and titrate upward every one to 2 weeks to the target dose.³ To help guide dosing decisions, use the estimated glomerular filtration rate (eGFR) instead of the serum creatinine (SCr) level, because the SCr can translate into a variable range of eGFRs (TABLE 1).^4,5

What if metformin alone isn't enough?

CASE › Richard C, age 50, has type 2 diabetes, hypertension, hyperlipidemia, and obesity. He takes metformin 1 g twice a day for his diabetes. After 3 months on this regimen, his HbA1c is 8.8%. How would you manage Mr. C's diabetes going forward?

If metformin at a maximum tolerated dose does not achieve the HbA1c target after 3 months, add a second oral agent (a sulfonylurea [SU], thiazolidinedione [TZD], dipeptidyl peptidase 4 [DPP-4] inhibitor, or sodium-glucose cotransporter-2 [SGLT2] inhibitor), a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal insulin (TABLE 2).¹

Factors that will affect the choice of the second agent include patient preference, cost, potential adverse effects, impact on weight, efficacy, and risk of hypoglycemia.

Based on cost, familiarity, and longstanding safety data, you decide to give Mr. C an SU, while cautioning him about hypoglycemia.

CASE › Mr. C has now been taking metformin and an SU at maximum doses for 2 years and continues with lifestyle modifications. Though his HbA1c level dropped after adding the SU, over 2 years it has crept up to 8.6% and his mean blood glucose is 186 mg/dL. What are your treatment options now?

If the target HbA1c level is not achieved on dual therapy, consider triple therapy combinations (TABLE 3).¹

In Mr. C's case, a third oral agent could be added, but DPP-4 and SGLT2 are unlikely to get his HbA1c below 7%. TZD may get his HbA1c into the desired range but is associated with adverse effects such as heart failure, edema, and weight gain. Mr. C agrees instead to start a basal insulin in conjunction with metformin. You could continue the SU, but you decide to stop it because the additive effect of these medications increases the risk of hypoglycemia.

CASE › Six months later Mr. C is taking metformin and insulin glargine, a basal insulin, adjusted to a fasting blood glucose of 80 to 130 mg/dL. His HbA1c is still above target at 8.4%, and the mean postprandial blood glucose is 232 mg/dL.

Mr. C is still above target for HbA1c and for postprandial blood glucose (goal: <180 mg/dL), so he needs pharmacotherapy that targets postprandial glucose elevations.¹ His fasting blood glucose readings are at goal, so increasing his insulin glargine is not recommended because it could cause hypoglycemia. An oral agent other than SU could be added, but none is potent enough to lower the HbA1c to goal (TABLE 2).¹ There are 3 other options:

• add a mealtime bolus of insulin
• add a GLP-1 receptor agonist
• switch to premixed (biphasic) insulin.

What to do when basal insulin isn’t enough—with or without oral medsFor type 2 diabetes poorly controlled on basal insulin with or without oral agents, the 2015 ADA treatment guidelines recommend adding a GLP-1 receptor agonist or mealtime insulin.¹ A less desirable alternative is to switch from basal insulin to a twice-daily premixed (biphasic) insulin analog (70/30 aspart mix or 75/25 or 50/50 lispro mix). The human NPH-Regular premixed formulations (70/30) are less costly alternatives. The disadvantage with all premixed insulins is they only cover 2 postprandial glucose elevations a day.^1,6,7

When prescribing medication for T2DM, consider efficacy, cost, tolerability, impact on body weight, comorbidities, risk of hypoglycemia, and patient preference.

Insulin requires multiple daily injections, can lead to weight gain, and carries the risk of hypoglycemia, which causes significant morbidity.^8,9 Daily or weekly administration of a GLP-1 receptor agonist combined with basal insulin can offer a more convenient alternative to mealtime boluses of insulin.

What are GLP-1 receptor agonists?

GLP-1 receptor agonists exert their maximum influence on blood glucose levels during the postprandial period by mimicking the body’s natural incretin hormonal response to oral glucose ingestion.¹⁰ They delay gastric emptying, promote satiety, decrease glucagon secretion, and increase insulin secretion.^10,11 This mechanism blunts the spiking of postprandial blood glucose after a meal and improves blood glucose control and weight reduction.^1,6,7

A systematic review and meta-analysis by Eng and colleagues compared the safety and efficacy of combined GLP-1 agonist and basal insulin with other treatment regimens.⁷ Fifteen randomized controlled trials were included involving 4348 participants with a mean trial duration of 25 weeks.

Compared with all other treatment regimens, the GLP-1 receptor agonist and basal insulin combination not only significantly reduced HbA1c by 0.44% (95% confidence interval [CI], -0.60 to -0.29) and increased the likelihood of attaining an HbA1c of <7.0% (relative risk [RR]=1.92; 95% CI, 1.43 to 2.56) but also reduced weight by 3.22 kg (-4.90 to -1.54) with no increased risk of hypoglycemia (RR=0.99; 0.76 to 1.29).⁷

GLP-1 agonist vs bolus insulin

Compared with basal-bolus insulin regimens, the combination of a GLP-1 receptor agonist with basal insulin has led to a significantly lowered risk of hypoglycemia (RR=0.67; 95% CI, 0.56 to 0.80), greater weight loss (-5.66 kg; 95% CI, -9.8 to -1.51) and an average reduction in HbA1c of 0.1% (95% CI, -0.17 to -0.02).⁷

There are 5 GLP-1 receptor agonists that have US Food and Drug Administration approval for the treatment of type 2 diabetes: albiglutide, dulaglutide, exenatide, exenatide XR, and liraglutide (TABLE 4).^3,12

All 5 agents are administered subcutaneously and packaged in pen-injector form. Adverse effects include nausea, which is transient and diminishes within the first few weeks of therapy, and less commonly, pancreatitis.^3,12

All of the GLP-1 receptor agonists, except short-acting exenatide, carry a warning about the risk of worsening renal function and a possible association with medullary thyroid carcinomas, which were identified in rats, but have not been observed in humans.^3,12 Medications in this drug class have a low risk for precipitating hypoglycemia.¹¹ Cost is their chief disadvantage, although copay reduction cards are available online for most of the products. Evaluate efficacy, ease of use, tolerability, and cost when selecting a GLP-1 receptor agonist.^3,12

CASE › Mr. C prefers a more convenient option than adding another daily injection. Given his obesity, a GLP-1 receptor agonist can help with weight loss and lower his risk for hypoglycemia. To further increase the convenience in dosing, you lean toward either weekly exenatide XR or dulaglutide over basal-bolus combination insulin. Weekly albiglutide is less potent than exenatide XR and dulaglutide in decreasing HbA1c.¹² Mr. C’s insurance plan provides preferred coverage for exenatide XR and he is eligible for a copay savings card, meaning he will pay no more than $25 per month for this new prescription. You prescribe exenatide XR and ask him to record his postprandial blood glucose levels. You follow up in one month to assess his response.

CORRESPONDENCE
Anne Mounsey, MD, University of North Carolina School of Medicine, Department of Family Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599; [email protected].

Illustrative case

Bob Z, age 48, presents to the emergency department (ED) with unspecified groin pain. A computed tomography scan of the kidney, ureter, and bladder (CT KUB) finds evidence of a single ureteral stone measuring 8 mm. He’s prescribed medication for the pain and discharged. The day after his ED visit, he comes to your office to discuss further treatment options. Should you prescribe tamsulosin or nifedipine to help him pass the stone?

The most recent National Health and Nutrition Examination Survey found kidney stones affect 8.8% of the population.² Outpatient therapy is indicated for patients with ureteric colic secondary to stones ≤10 mm who do not have uncontrolled pain, impaired kidney function, or severe infection. Routine outpatient care includes oral hydration, antiemetics, and pain medications. Medical expulsive therapy (MET) is also used to facilitate stone passage. MET is increasingly becoming part of routine care; use of MET in kidney stone patients in the United States has grown from 14% in 2009 to 64% in 2012.^3,4

The joint European Association of Urology/American Urological Association Nephrolithiasis Guideline Panel supports the use of MET.⁵ Meta-analyses of multiple randomized controlled trials (RCTs) suggest that an alpha-blocker (tamsulosin) or a calcium channel blocker (nifedipine) can reduce pain and lead to quicker stone passage and a higher rate of eventual stone passage when compared to placebo or observation.^6,7 However, these reviews included small, heterogeneous studies with a high or unclear risk of bias.

Treatment with tamsulosin or nifedipine provided no benefits in terms of rate of kidney stone passage, time to passage, analgesic use, or pain.

STUDY SUMMARY: MET doesn’t increase the rate of stone passage

The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial¹ was a multicenter RCT designed to determine the effectiveness of tamsulosin or nifedipine as MET for patients ages 18 to 65 years with a single ureteric stone measuring ≤10 mm on CT KUB, which has 98% diagnostic accuracy.⁸ (Stones >10 mm typically require surgery or lithotripsy.)

In this RCT, 1167 adults were randomized to take tamsulosin 0.4 mg/d, nifedipine 30 mg/d, or placebo for 4 weeks or until the stone spontaneously passed, whichever came first. The participants, clinicians, and research staff were blinded to treatment assignment. The primary outcome was the proportion of participants who spontaneously passed their stone, as indicated in patient self-reported questionnaires and case-report forms completed by researchers. Secondary outcomes were time to stone passage and pain as assessed by analgesic use and a visual analogue scale (VAS).

At 4 weeks, 1136 (97%) of the randomized participants had data available for analysis. The proportion of participants who passed their stone did not differ between MET and placebo; 80% of the placebo group (303 of 379 participants) passed the stone, compared with 81% (307 of 378) of the tamsulosin group and 80% (304 of 379) of the nifedipine group. The odds ratio (OR) for MET vs placebo was 1.04 (95% confidence interval [CI], 0.77 to 1.43) and the OR for tamsulosin vs nifedipine was 1.07 (95% CI, 0.74 to 1.53). These findings did not change with further subgroup analysis, including by sex, stone size (≤5 mm vs >5 mm), or stone location.

There were no differences between groups in time to stone passage as measured by clinical report and confirmed by imaging. Time to passage of stone was available for 237 (21%) of participants. The mean days to stone passage was 15.9 (n=84) for placebo, 16.5 (n=79) for tamsulosin and 16.2 (n=74) for nifedipine, with a MET vs placebo difference of 0.5 days (95% CI, -2.9 to 3.9; P=.78). Sensitivity analysis accounting for bias from missing data did not change this outcome.

No differences in analgesic use or pain. Self-reported use of pain medication during the first 4 weeks was similar between groups: 59% (placebo patients), 56% (tamsulosin), and 56% (nifedipine). The mean days of pain medication use was 10.5 for placebo, 11.6 for tamsulosin, and 10.7 for nifedipine, with a MET vs placebo difference of 0.6 days (95% CI, -1.6 to 2.8; P=.45).

There was no difference between groups in the VAS pain score at 4 weeks. The MET vs placebo difference was 0.0 (95% CI, -0.4 to 0.4; P=.96) and the mean VAS pain score was 1.2 for placebo, 1.0 for tamsulosin, and 1.3 for nifedipine.

WHAT'S NEW: This large RCT contradicts results from previous meta-analyses

The SUSPEND study is the first large, multi­center RCT of MET with tamsulosin or nifedipine for kidney stones that used patient-oriented outcomes to find no benefit for stone expulsion, analgesic use, or reported pain compared to placebo. The discrepancy with prior meta-analyses is not unusual. Up to one-third of meta-analyses that show positive outcomes of a therapy are subsequently altered by the inclusion of results from a single, large, multicenter, well-designed RCT.⁹

CAVEATS: This trial included fewer women than previous studies

The SUSPEND study included a smaller proportion of women than previously published case series due to a need for a diagnostic CT KUB, which excluded more women than men due to radiation concerns. However, the proportion of women was balanced across all groups in this trial, and there was no evidence that sex impacted the efficacy of treatment for the primary outcome.¹

CHALLENGES TO IMPLEMENTATION

We see no challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

Illustrative case

Bob Z, age 48, presents to the emergency department (ED) with unspecified groin pain. A computed tomography scan of the kidney, ureter, and bladder (CT KUB) finds evidence of a single ureteral stone measuring 8 mm. He’s prescribed medication for the pain and discharged. The day after his ED visit, he comes to your office to discuss further treatment options. Should you prescribe tamsulosin or nifedipine to help him pass the stone?

The most recent National Health and Nutrition Examination Survey found kidney stones affect 8.8% of the population.² Outpatient therapy is indicated for patients with ureteric colic secondary to stones ≤10 mm who do not have uncontrolled pain, impaired kidney function, or severe infection. Routine outpatient care includes oral hydration, antiemetics, and pain medications. Medical expulsive therapy (MET) is also used to facilitate stone passage. MET is increasingly becoming part of routine care; use of MET in kidney stone patients in the United States has grown from 14% in 2009 to 64% in 2012.^3,4

The joint European Association of Urology/American Urological Association Nephrolithiasis Guideline Panel supports the use of MET.⁵ Meta-analyses of multiple randomized controlled trials (RCTs) suggest that an alpha-blocker (tamsulosin) or a calcium channel blocker (nifedipine) can reduce pain and lead to quicker stone passage and a higher rate of eventual stone passage when compared to placebo or observation.^6,7 However, these reviews included small, heterogeneous studies with a high or unclear risk of bias.

Treatment with tamsulosin or nifedipine provided no benefits in terms of rate of kidney stone passage, time to passage, analgesic use, or pain.

STUDY SUMMARY: MET doesn’t increase the rate of stone passage

The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial¹ was a multicenter RCT designed to determine the effectiveness of tamsulosin or nifedipine as MET for patients ages 18 to 65 years with a single ureteric stone measuring ≤10 mm on CT KUB, which has 98% diagnostic accuracy.⁸ (Stones >10 mm typically require surgery or lithotripsy.)

In this RCT, 1167 adults were randomized to take tamsulosin 0.4 mg/d, nifedipine 30 mg/d, or placebo for 4 weeks or until the stone spontaneously passed, whichever came first. The participants, clinicians, and research staff were blinded to treatment assignment. The primary outcome was the proportion of participants who spontaneously passed their stone, as indicated in patient self-reported questionnaires and case-report forms completed by researchers. Secondary outcomes were time to stone passage and pain as assessed by analgesic use and a visual analogue scale (VAS).

At 4 weeks, 1136 (97%) of the randomized participants had data available for analysis. The proportion of participants who passed their stone did not differ between MET and placebo; 80% of the placebo group (303 of 379 participants) passed the stone, compared with 81% (307 of 378) of the tamsulosin group and 80% (304 of 379) of the nifedipine group. The odds ratio (OR) for MET vs placebo was 1.04 (95% confidence interval [CI], 0.77 to 1.43) and the OR for tamsulosin vs nifedipine was 1.07 (95% CI, 0.74 to 1.53). These findings did not change with further subgroup analysis, including by sex, stone size (≤5 mm vs >5 mm), or stone location.

There were no differences between groups in time to stone passage as measured by clinical report and confirmed by imaging. Time to passage of stone was available for 237 (21%) of participants. The mean days to stone passage was 15.9 (n=84) for placebo, 16.5 (n=79) for tamsulosin and 16.2 (n=74) for nifedipine, with a MET vs placebo difference of 0.5 days (95% CI, -2.9 to 3.9; P=.78). Sensitivity analysis accounting for bias from missing data did not change this outcome.

No differences in analgesic use or pain. Self-reported use of pain medication during the first 4 weeks was similar between groups: 59% (placebo patients), 56% (tamsulosin), and 56% (nifedipine). The mean days of pain medication use was 10.5 for placebo, 11.6 for tamsulosin, and 10.7 for nifedipine, with a MET vs placebo difference of 0.6 days (95% CI, -1.6 to 2.8; P=.45).

There was no difference between groups in the VAS pain score at 4 weeks. The MET vs placebo difference was 0.0 (95% CI, -0.4 to 0.4; P=.96) and the mean VAS pain score was 1.2 for placebo, 1.0 for tamsulosin, and 1.3 for nifedipine.

WHAT'S NEW: This large RCT contradicts results from previous meta-analyses

The SUSPEND study is the first large, multi­center RCT of MET with tamsulosin or nifedipine for kidney stones that used patient-oriented outcomes to find no benefit for stone expulsion, analgesic use, or reported pain compared to placebo. The discrepancy with prior meta-analyses is not unusual. Up to one-third of meta-analyses that show positive outcomes of a therapy are subsequently altered by the inclusion of results from a single, large, multicenter, well-designed RCT.⁹

CAVEATS: This trial included fewer women than previous studies

The SUSPEND study included a smaller proportion of women than previously published case series due to a need for a diagnostic CT KUB, which excluded more women than men due to radiation concerns. However, the proportion of women was balanced across all groups in this trial, and there was no evidence that sex impacted the efficacy of treatment for the primary outcome.¹

CHALLENGES TO IMPLEMENTATION

We see no challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

Illustrative case

Bob Z, age 48, presents to the emergency department (ED) with unspecified groin pain. A computed tomography scan of the kidney, ureter, and bladder (CT KUB) finds evidence of a single ureteral stone measuring 8 mm. He’s prescribed medication for the pain and discharged. The day after his ED visit, he comes to your office to discuss further treatment options. Should you prescribe tamsulosin or nifedipine to help him pass the stone?

The most recent National Health and Nutrition Examination Survey found kidney stones affect 8.8% of the population.² Outpatient therapy is indicated for patients with ureteric colic secondary to stones ≤10 mm who do not have uncontrolled pain, impaired kidney function, or severe infection. Routine outpatient care includes oral hydration, antiemetics, and pain medications. Medical expulsive therapy (MET) is also used to facilitate stone passage. MET is increasingly becoming part of routine care; use of MET in kidney stone patients in the United States has grown from 14% in 2009 to 64% in 2012.^3,4

The joint European Association of Urology/American Urological Association Nephrolithiasis Guideline Panel supports the use of MET.⁵ Meta-analyses of multiple randomized controlled trials (RCTs) suggest that an alpha-blocker (tamsulosin) or a calcium channel blocker (nifedipine) can reduce pain and lead to quicker stone passage and a higher rate of eventual stone passage when compared to placebo or observation.^6,7 However, these reviews included small, heterogeneous studies with a high or unclear risk of bias.

Treatment with tamsulosin or nifedipine provided no benefits in terms of rate of kidney stone passage, time to passage, analgesic use, or pain.

STUDY SUMMARY: MET doesn’t increase the rate of stone passage

The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial¹ was a multicenter RCT designed to determine the effectiveness of tamsulosin or nifedipine as MET for patients ages 18 to 65 years with a single ureteric stone measuring ≤10 mm on CT KUB, which has 98% diagnostic accuracy.⁸ (Stones >10 mm typically require surgery or lithotripsy.)

In this RCT, 1167 adults were randomized to take tamsulosin 0.4 mg/d, nifedipine 30 mg/d, or placebo for 4 weeks or until the stone spontaneously passed, whichever came first. The participants, clinicians, and research staff were blinded to treatment assignment. The primary outcome was the proportion of participants who spontaneously passed their stone, as indicated in patient self-reported questionnaires and case-report forms completed by researchers. Secondary outcomes were time to stone passage and pain as assessed by analgesic use and a visual analogue scale (VAS).

At 4 weeks, 1136 (97%) of the randomized participants had data available for analysis. The proportion of participants who passed their stone did not differ between MET and placebo; 80% of the placebo group (303 of 379 participants) passed the stone, compared with 81% (307 of 378) of the tamsulosin group and 80% (304 of 379) of the nifedipine group. The odds ratio (OR) for MET vs placebo was 1.04 (95% confidence interval [CI], 0.77 to 1.43) and the OR for tamsulosin vs nifedipine was 1.07 (95% CI, 0.74 to 1.53). These findings did not change with further subgroup analysis, including by sex, stone size (≤5 mm vs >5 mm), or stone location.

There were no differences between groups in time to stone passage as measured by clinical report and confirmed by imaging. Time to passage of stone was available for 237 (21%) of participants. The mean days to stone passage was 15.9 (n=84) for placebo, 16.5 (n=79) for tamsulosin and 16.2 (n=74) for nifedipine, with a MET vs placebo difference of 0.5 days (95% CI, -2.9 to 3.9; P=.78). Sensitivity analysis accounting for bias from missing data did not change this outcome.

No differences in analgesic use or pain. Self-reported use of pain medication during the first 4 weeks was similar between groups: 59% (placebo patients), 56% (tamsulosin), and 56% (nifedipine). The mean days of pain medication use was 10.5 for placebo, 11.6 for tamsulosin, and 10.7 for nifedipine, with a MET vs placebo difference of 0.6 days (95% CI, -1.6 to 2.8; P=.45).

There was no difference between groups in the VAS pain score at 4 weeks. The MET vs placebo difference was 0.0 (95% CI, -0.4 to 0.4; P=.96) and the mean VAS pain score was 1.2 for placebo, 1.0 for tamsulosin, and 1.3 for nifedipine.

WHAT'S NEW: This large RCT contradicts results from previous meta-analyses

The SUSPEND study is the first large, multi­center RCT of MET with tamsulosin or nifedipine for kidney stones that used patient-oriented outcomes to find no benefit for stone expulsion, analgesic use, or reported pain compared to placebo. The discrepancy with prior meta-analyses is not unusual. Up to one-third of meta-analyses that show positive outcomes of a therapy are subsequently altered by the inclusion of results from a single, large, multicenter, well-designed RCT.⁹

CAVEATS: This trial included fewer women than previous studies

The SUSPEND study included a smaller proportion of women than previously published case series due to a need for a diagnostic CT KUB, which excluded more women than men due to radiation concerns. However, the proportion of women was balanced across all groups in this trial, and there was no evidence that sex impacted the efficacy of treatment for the primary outcome.¹

CHALLENGES TO IMPLEMENTATION

We see no challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY